2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T793,In NSCLC, TP53 mutations are heterogeneous with varied effects on protein synthesis, function and clinical outcomes. We hypothesize that a refined classification of TP53 mutations, beyond binary categorization, could improve prognostication. Furthermore, specific mutations could be associated with enhanced benefit from immune checkpoint inhibitors (ICI) versus chemotherapy. To investigate this, we analyzed data from randomized trials (OAK and POPLAR) which compared atezolizumab to chemotherapy in previously treated advanced driver-negative NSCLC. Participants were classified as TP53 mutant or wild-type using baseline plasma, and by coding mutation, and Olivier's and Poeta's classification. We performed multivariable Cox regression analyses to evaluate the prognostic significance of TP53 mutations, and interaction tests to assess their predictive value. Among 762 participants, 49% harbored a TP53 mutation. TP53 mutations based on binary categorization were associated with poorer but not statistically significant OS compared to wild-type (adjusted-HR 1.15; 95 %CI 0.96-1.38; P = .12). However, nonsense mutations classified by coding mutations (adjusted-HR 1.71; 95% CI 1.22-2.39;P = .002), non-missense mutations classified by Olivier's classification (adjusted-HR 1.33; 95% CI 1.03-1.74; P = .03) and disruptive mutations classified by Poeta's classification (adjusted-HR 1.33; 95% CI 1.37-1.77; P = .03) were associated with statistically significant poorer OS. TP53 status did not predict differential benefit from ICI versus chemotherapy (interaction P = .45). In advanced driver-negative NSCLC following progression on first-line chemotherapy, nonsense, non-missense and disruptive mutations of TP53 were strongly associated with inferior OS. These data support utilizing a nuanced classification of TP53 mutations as a stratification factor in future trials, and laboratory reporting to aid prognostication.31:T54d,Immune checkpoint blockade-based multimodal therapy is widely used across oncology; yet drivers of resistance in most cancer types are not well understood. Here, we comprehensively characterized the tumor genome, microenvironment and microbiome in a phase 3 international randomized trial ( NCT02952586 ) to identify factors that shape outcomes to anti-PD-L1 avelumab plus standard-of-care chemoradiotherapy versus placebo/chemoradiotherapy in individuals with locally advanced head and neck cancer. Patients receiving avelumab whose tumors contained distinct immunologic and genetic features had superior outcomes compared to those receiving placebo. By contrast, patients with increased myeloid/neutrophil activities had worse outcomes with avelumab than those treated with placebo. Strikingly, these tumors possessed telltale intratumoral bacteria, elevated tumor-associated neutrophils, high systemic neutrophil-to-lymphocyte ratios and suppressed adaptive immunity. We define tumor ecosystems associated with benefit to chemoimmunotherapy. Our data demonstrate how intratumoral bacteria affect immune checkpoint blockade response within a randomized trial. These discoveries enhance our understanding of combination immunotherapy, provide a useful multiomic resource and identify unanticipated interactions that may guide future therapeutic strategies.32:T4b0,Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation or reduction in intratumoral bacteria abundance in orthotopic models of HNSCC in female mice recapitulated immunological associations observed in participant tumors. Increasing intratumoral bacteria abundance was sufficient to induce resistance to anti-PDL1 ICB, irrespective of bacterial species tested. Together, these findings demonstrate that high intratumoral bacteria abundance is a key suppressor of antitumor immunity and promotes immunotherapy resistance.33:T5e0,Abstract Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation or reduction in intratumoral bacteria abundance in orthotopic models of HNSCC in female mice recapitulated immunological associations observed in participant tumors. Increasing intratumoral bacteria abundance was sufficient to induce resistance to anti-PDL1 ICB, irrespective of bacterial species tested. Together, these findings demonstrate that high intratumoral bacteria abundance is a key suppressor of antitumor immunity and promotes immunotherapy resistance. 34:T5d0,T.A.C. is a cofounder of Gritstone Oncology and holds equity. T.A.C. holds equity in An2H. T.A.C. acknowledges grant funding from Bristol-Myers Squibb, AstraZeneca, Illumina, Pfizer, An2H and Eisai. T.A.C. has served as an advisor for Bristol-Myers, MedImmune, Squibb, Illumina, Eisai, AstraZeneca and An2H. T.A.C. is an inventor on intellectual property held by Memorial Sloan Kettering Cancer Center on using TMB to predict immunotherapy response, with a pending patent, which has been licensed to PGDx. E.J.S. consults for Siren Biotechnology and has immunotherapy patent applications under option to license agreements with iOncologi. N.G. reports grants or contracts and personal or consulting fees from Regeneron Pharmaceuticals, personal or consulting fees from DragonFly Therapeutics, Intuitive Surgical, Merck, Replimune and Sanofi/Genzyme US Companies and support for other professional activities from PDS Biotechnology Corporation outside the submitted work. R.F. reports consulting or advisory roles for Regeneron, Sanofi, Ayala Pharmaceuticals, Prelude Therapeutics, Elevar Therapeutics, G1 Therapeutics, Guidepoint, Expert Connect, Remix, Eisai and Bioatlas in the past 24 months and research funds from Prelude, Ayala, Merck, Genentech, Pfizer, Rakuten, Nanobiotix, EMD Serono, ISA, Viracta and Gilead in the past 24 months. D.J.M. holds intellectual property for transcriptional signatures to predict response to ICB. The other authors declare no competing interests.35:T8a2,Tertiary lymphoid structures (TLS) are ectopic lymphoid formations within or around tumours, emerging as important predictors of prognosis and response to immune checkpoint inhibitors (ICI) in various cancers. However, in Merkel cell carcinoma (MCC), the correlation between TLS and ICI response has not yet been evaluated. Furthermore, the criteria for assessing TLS maturity vary by report, and there is no unified consensus. In this study, we investigated the relationship between TLS and ICI responsiveness in MCC using spatial proteomics at the single-cell level. By comparing the spatial characteristics of TLS in ICI responders and non-responders, we also aimed to identify features related to functionality of TLS, distinct from the previously reported maturity of TLS. We analysed 24 TLSs from 13 MCC cases treated with the anti-PD-L1 antibody, avelumab, employing the PhenoCycler platform with 16 oligonucleotide-labeled antibodies. Infiltrating immune cells and tumour cells were phenotyped based on machine learning, and spatial single-cell analysis was performed, including cellular neighbourhood analysis and cell-cell correlation analysis. Our findings revealed that the number of TLS positively correlated with survival and ICI response (p=0.0274). The number of TLS observed within the tumour was significantly higher in responders than in non-responders (p=0.0043). Cellular neighbourhood analysis and cell-cell correlation analysis demonstrated that in functional TLS in responder cases, T cells infiltrated densely within B cell clusters, extending close to follicular dendritic cells, and CD4-positive T cells adjacent to CD8-positive T cells express PD1. In contrast, in non-responder TLS, although B cell density is high, T cells did not infiltrate into B cell cluster areas but instead resided in the peripheral areas. Furthermore, it was found that CD8-positive T cells and CD4-positive T cells approaching B cells expressed PD1. This study demonstrated a significant positive correlation between the number of TLS and ICI response in MCC. Additionally, our results suggest that the immune composition and spatial configuration within TLS may be important determinants of ICI efficacy.36:Tbb6,Abstract Background Tertiary lymphoid structures (TLS) are ectopic lymphoid formations within or around tumours, emerging as important predictors of prognosis and response to immune checkpoint inhibitors (ICI) in various cancers. However, in Merkel cell carcinoma (MCC), the correlation between TLS and ICI response has not yet been evaluated. Furthermore, the criteria for assessing TLS maturity vary by report, and there is no unified consensus. Objective In this study, we investigated the relationship between TLS and ICI responsiveness in MCC using spatial proteomics at the single-cell level. By comparing the spatial characteristics of TLS in ICI responders and non-responders, we also aimed to identify features related to functionality of TLS, distinct from the previously reported maturity of TLS. Methods We analysed 24 TLSs from 13 MCC cases treated with the anti-PD-L1 antibody, avelumab, employing the PhenoCycler platform with 16 oligonucleotide-labeled antibodies. Infiltrating immune cells and tumour cells were phenotyped based on machine learning, and spatial single-cell analysis was performed, including cellular neighbourhood analysis and cell-cell correlation analysis. Results Our findings revealed that the number of TLS positively correlated with survival and ICI response (p=0.0274). The number of TLS observed within the tumour was significantly higher in responders than in non-responders (p=0.0043). Cellular neighbourhood analysis and cell-cell correlation analysis demonstrated that in functional TLS in responder cases, T cells infiltrated densely within B cell clusters, extending close to follicular dendritic cells, and CD4-positive T cells adjacent to CD8-positive T cells express PD1. In contrast, in non-responder TLS, although B cell density is high, T cells did not infiltrate into B cell cluster areas but instead resided in the peripheral areas. Furthermore, it was found that CD8-positive T cells and CD4-positive T cells approaching B cells expressed PD1. Conclusions This study demonstrated a significant positive correlation between the number of TLS and ICI response in MCC. Additionally, our results suggest that the immune composition and spatial configuration within TLS may be important determinants of ICI efficacy. 37:T733,Emerging evidence suggests that circadian timing influences the efficacy of immune checkpoint inhibitors (ICI), with morning infusions associated with improved therapeutic outcomes across various malignancies. However, the impact of ICI infusion timing on extensive-stage small cell lung cancer (ES-SCLC), a disease with poor prognosis and limited therapeutic advancements, remains unexplored. This retrospective study (LungTime-R02) analyzed 397 patients with ES-SCLC who received first-line anti-PD-L1 (atezolizumab or durvalumab) plus chemotherapy at our center between May 2019 and October 2023. The time of day of administration (ToDA) was calculated as the median infusion time for each patient's first four ICI treatment cycles. To assess its prognostic relevance, hazard ratios (HRs) of earlier progression or death were estimated across multiple ToDA thresholds (11:00-16:30). Propensity score matching (1:2) was applied to balance baseline characteristics. Of the 397 patients, the optimal ToDA cutoff for maximizing progression-free survival (PFS) benefit was identified as 15:00, with the lowest HR for PFS observed at this threshold. Patients who received immunochemotherapy before 15:00 exhibited significantly longer PFS and overall survival compared to those treated later, with results consistent across pooled and propensity score matching cohorts. Multivariable analysis confirmed early ToDA as an independent prognostic factor for both PFS (adjusted HR, 0.483; 95% CI, 0.357-0.654) and overall survival (adjusted HR, 0.373; 95% CI, 0.265-0.526). This study provides real-world evidence supporting the survival benefit of earlier immunochemotherapy administration in patients with ES-SCLC. These findings add to the growing body of knowledge on the clinical relevance of circadian timing in cancer treatment. Not applicable.38:Ta71,Abstract Background Emerging evidence suggests that circadian timing influences the efficacy of immune checkpoint inhibitors (ICI), with morning infusions associated with improved therapeutic outcomes across various malignancies. However, the impact of ICI infusion timing on extensive‐stage small cell lung cancer (ES‐SCLC), a disease with poor prognosis and limited therapeutic advancements, remains unexplored. Method This retrospective study (LungTime‐R02) analyzed 397 patients with ES‐SCLC who received first‐line anti–PD‐L1 (atezolizumab or durvalumab) plus chemotherapy at our center between May 2019 and October 2023. The time of day of administration (ToDA) was calculated as the median infusion time for each patient’s first four ICI treatment cycles. To assess its prognostic relevance, hazard ratios (HRs) of earlier progression or death were estimated across multiple ToDA thresholds (11:00–16:30). Propensity score matching (1:2) was applied to balance baseline characteristics. Result Of the 397 patients, the optimal ToDA cutoff for maximizing progression‐free survival (PFS) benefit was identified as 15:00, with the lowest HR for PFS observed at this threshold. Patients who received immunochemotherapy before 15:00 exhibited significantly longer PFS and overall survival compared to those treated later, with results consistent across pooled and propensity score matching cohorts. Multivariable analysis confirmed early ToDA as an independent prognostic factor for both PFS (adjusted HR, 0.483; 95% CI, 0.357–0.654) and overall survival (adjusted HR, 0.373; 95% CI, 0.265–0.526). Conclusion This study provides real‐world evidence supporting the survival benefit of earlier immunochemotherapy administration in patients with ES‐SCLC. These findings add to the growing body of knowledge on the clinical relevance of circadian timing in cancer treatment. CLINICAL TRIAL REGISTRATION Not applicable 39:T517,Cosibelimab-ipdl, a high-affinity, programmed death-ligand 1-blocking antibody, is approved by the US Food and Drug Administration for treatment of adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or radiation. To report long-term efficacy and safety outcomes from a pivotal study of cosibelimab in mCSCC or laCSCC. Patients received intravenous cosibelimab 800 mg every 2 weeks (mCSCC and laCSCC cohorts) or 1200 mg every 3 weeks (mCSCC cohort). The primary endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DOR) and safety. With a median follow-up duration of 29.3 months for the mCSCC cohort (n = 78), ORR was 50.0% (complete response [CR], 12.8%), median DOR was not reached, and estimated 24-month DOR was 72.1%. With a median follow-up duration of 24.1 months for the laCSCC cohort (n = 31), ORR was 54.8% (CR, 25.8%), median DOR was not reached, and the estimated 24-month DOR was 80.2%. Immune-related adverse event rate was 27.6%; 3.6% grade 3, no grade ≥4 events. Nonrandomized; limited biomarker analysis. Cosibelimab demonstrated robust and durable ORRs with increasing CR rates in advanced CSCC and low rates of severe immune-related adverse events.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"PD-L1 Inhibitor: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on PD-L1 Inhibitor (modality). 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Direct comparison to checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies) is not reported. Long-term safety and pharmacokinetics in vivo are not fully characterized.","practice_takeaway":"PSEs are not yet in clinical use, but their bifunctional design — bridging innate phagocytosis enhancement with adaptive checkpoint modulation — offers a potential strategy for 'cold,' macrophage-rich tumors like colorectal and pancreatic cancer that currently respond poorly to immunotherapy. Clinicians should watch for early-phase trials evaluating this or similar innate-adaptive co-targeting platforms."}},{"doi":"10.1016/s2468-1253(26)00212-8","pmid":"42641632","title":"On-demand transarterial chemoembolisation combined with atezolizumab and bevacizumab in patients with untreated hepatocellular carcinoma (TALENTACE): a multicentre, randomised, open-label, phase 3 trial","journal_title":"The Lancet Gastroenterology & Hepatology","journal_issn":"2468-1253","published_at":"2026-08-25T00:00:00.000Z","url":"https://doi.org/10.1016/s2468-1253(26)00212-8","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-03T06:19:57.310Z","updated_at":"2026-09-03T06:19:57.310Z","tags":[{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"brand","value":"Avastin","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"brand","value":"Tecentriq","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"generic","value":"atezolizumab","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"generic","value":"bevacizumab","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"modality","value":"Anti-VEGF Antibody","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"modality","value":"Transarterial Chemoembolisation","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"sample_size","value":"n=342","value_numeric":342},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"warning","value":"Overall survival data are immature at this publication; the OS result (HR 0.96) should be interpreted cautiously and not used as a primary efficacy conclusion.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"warning","value":"TACE-PFS is a surrogate endpoint specific to this trial; it is not a universally standardised oncology endpoint, which may complicate cross-trial comparisons.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"warning","value":"The brand name 'Tecentriq' is used for atezolizumab; availability and labelling may vary by region.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00212-8","tag_type":"warning","value":"The trial enrolled almost exclusively Asian patients (90% Chinese, 10% Japanese), which may limit applicability to non-Asian populations.","value_numeric":null}],"summaries":{"what_studied":"This phase 3 RCT (TALENTACE) evaluated on-demand TACE plus atezolizumab (1200 mg IV) and bevacizumab (15 mg/kg IV) every 3 weeks versus on-demand TACE alone in 342 patients with untreated, intermediate-to-high tumour burden unresectable HCC (six-and-twelve score ≥6) across 40 centres in China and Japan, with a median follow-up of 26.25 months.","key_result":"Adding atezolizumab + bevacizumab to on-demand TACE significantly improved TACE-PFS: median 11.30 months vs. 7.03 months (HR 0.71, 95% CI 0.55–0.92; p=0.0089). Overall survival remained immature at the first interim analysis (median ~34.5 vs. ~35.4 months; HR 0.96, 99.62% CI 0.58–1.58), with no significant difference yet observed.","limitations":"- Overall survival data are immature and no OS benefit has been demonstrated at this interim analysis.\n- Trial was conducted exclusively in China and Japan (90% Chinese), limiting generalisability to Western populations.\n- Open-label design introduces potential performance and assessment bias.","practice_takeaway":"For patients with intermediate-to-high tumour burden unresectable HCC, combining on-demand TACE with atezolizumab + bevacizumab meaningfully delays untreatable progression compared to TACE alone. However, an OS benefit has not yet been confirmed—clinicians should weigh the improved TACE-PFS against the added toxicity burden (notably hypertension 14%, thrombocytopenia 14%, and 5 treatment-related deaths) while awaiting mature OS data."}},{"doi":"10.1016/s1470-2045(26)00278-0","pmid":"42636832","title":"Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study","journal_title":"The Lancet Oncology","journal_issn":"1470-2045","published_at":"2026-08-24T00:00:00.000Z","url":"https://doi.org/10.1016/s1470-2045(26)00278-0","source_score":41,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-05T06:20:12.076Z","updated_at":"2026-09-05T06:20:12.076Z","tags":[{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"brand","value":"Imfinzi","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"generic","value":"durvalumab","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"generic","value":"lenvatinib","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"generic","value":"tremelimumab","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"modality","value":"CTLA-4 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"modality","value":"Transarterial Chemoembolisation","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"sample_size","value":"n=760","value_numeric":760},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"warning","value":"Brand tag 'Imfinzi' applies to durvalumab; tremelimumab's brand name (Imjudo) was not mentioned in the source text and was therefore omitted.","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"warning","value":"OS data are immature at time of publication — the primary PFS endpoint was met but OS did not reach statistical significance; final OS analysis is ongoing.","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"warning","value":"TACE procedures were not standardised (technique and frequency per investigator discretion), which may limit generalisability and introduces heterogeneity across sites.","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"warning","value":"The 'practice_changing' flag is applied cautiously: PFS improvement is statistically significant, but confirmed OS benefit is absent at this interim analysis.","value_numeric":null}],"summaries":{"what_studied":"This phase 3 RCT (EMERALD-3) evaluated STRIDE (single-dose tremelimumab 300 mg + durvalumab 1500 mg, then durvalumab every 4 weeks), with or without lenvatinib, combined with TACE versus TACE alone in 760 adults with embolisation-eligible HCC not amenable to curative therapy, across 177 sites in 21 countries.","key_result":"STRIDE + lenvatinib + TACE significantly improved median PFS vs TACE alone (13.0 vs 9.8 months; HR 0.70, 95% CI 0.57–0.86; p=0.0007), but median OS did not reach statistical significance (39.5 vs 34.7 months; HR 0.84, 95% CI 0.65–1.09; p=0.18). STRIDE + TACE also improved PFS vs TACE (12.9 vs 8.1 months; HR 0.71, 95% CI 0.56–0.91). Serious adverse events were more common in combination arms (64% and 51%) than TACE alone (23%); treatment-related deaths occurred in 7 (2%) patients on STRIDE + lenvatinib + TACE.","limitations":"- OS data are immature (final analysis pending); the OS result did not reach statistical significance at interim analysis.\n- Open-label design with sponsor blinding only may introduce performance or assessment bias.\n- TACE technique and number of procedures were left to investigator discretion, introducing heterogeneity.","practice_takeaway":"STRIDE + lenvatinib + TACE improves PFS in embolisation-eligible HCC and may represent a new combination option, but the OS benefit is not yet confirmed — clinicians should weigh this against a meaningfully higher serious adverse event burden (64% vs 23%) and treatment-related mortality risk before routine adoption."}},{"doi":"10.1016/j.lungcan.2026.109583","pmid":"42636548","title":"Daily low-dose carboplatin or weekly carboplatin plus nab-paclitaxel for concurrent chemoradiotherapy in older patients with locally advanced non-small cell lung cancer (JCOG1914): A randomized phase 3 trial","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-08-14T00:00:00.000Z","url":"https://doi.org/10.2139/ssrn.5829100","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-27T06:17:03.680Z","updated_at":"2026-08-27T06:17:03.680Z","tags":[{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"brand","value":"Abraxane","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"brand","value":"Imfinzi","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"condition","value":"Locally Advanced Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"generic","value":"carboplatin","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"generic","value":"durvalumab","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"generic","value":"nab-paclitaxel","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"modality","value":"Chemoradiotherapy","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"modality","value":"Platinum Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"modality","value":"Taxane","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"sample_size","value":"n=124","value_numeric":124},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"warning","value":"The non-inferiority design means the study was not powered to detect superiority; the HR of 1.56 trending against the combination arm should be noted clinically even though p=0.200.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"warning","value":"The study was conducted exclusively in Japan (≥75 years), which may limit applicability to other ethnic groups or health systems with different treatment thresholds for older adults.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109583","tag_type":"warning","value":"Trial was terminated early for futility after interim analysis; final OS data are immature (median not reached in control arm), so survival estimates should be interpreted cautiously.","value_numeric":null}],"summaries":{"what_studied":"This open-label randomized phase 3 trial (JCOG1914) compared daily low-dose carboplatin (30 mg/m²) vs. weekly carboplatin (AUC 2) plus nab-paclitaxel (30 mg/m²), each with concurrent thoracic radiotherapy and optional durvalumab maintenance, in patients aged ≥75 years with unresectable locally advanced NSCLC across 38 Japanese institutions (December 2020–March 2024).","key_result":"The trial was stopped early for futility: Bayesian predictive probability of non-inferiority for carboplatin + nab-paclitaxel was only 8.0%. Median OS was not reached in the carboplatin-alone arm vs. 26.1 months in the combination arm (HR 1.56; 95% CI 0.79–3.11; p=0.200). The carboplatin-alone arm also had significantly better quality of life at 6 weeks (OR 0.39; 95% CI 0.18–0.81; p=0.012). Two treatment-related deaths and seven non-cancer-related deaths occurred in the combination arm.","limitations":"- Trial stopped early for futility with only 124 patients enrolled, limiting statistical power for definitive OS conclusions.\n- Single-country (Japan) study population may limit generalizability.\n- Median OS was not yet reached in the control arm, making survival comparisons preliminary.","practice_takeaway":"For patients aged ≥75 with unresectable LA-NSCLC, daily low-dose carboplatin with concurrent thoracic radiotherapy remains the standard of care — adding weekly nab-paclitaxel did not improve survival and worsened quality of life. Clinicians should not adopt the carboplatin + nab-paclitaxel regimen in this older population."}},{"doi":"10.1200/jco-25-03052","pmid":"42525921","title":"COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-07-29T00:00:00.000Z","url":"https://doi.org/10.1200/jco-25-03052","source_score":62,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:18:09.513Z","updated_at":"2026-08-04T18:18:09.513Z","tags":[{"paper_doi":"10.1200/jco-25-03052","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"brand","value":"Avastin","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"brand","value":"Tecentriq","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"condition","value":"Metastatic Colorectal Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"condition","value":"Mismatch Repair Deficient / Microsatellite Instability-High Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"generic","value":"atezolizumab","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"generic","value":"bevacizumab","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"generic","value":"fluorouracil","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"generic","value":"leucovorin","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"generic","value":"oxaliplatin","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"modality","value":"VEGF Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"sample_size","value":"n=102","value_numeric":102},{"paper_doi":"10.1200/jco-25-03052","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"warning","value":"Atezolizumab (PD-L1 inhibitor) is the comparator, not a currently approved standard (pembrolizumab or nivolumab); extrapolation to PD-1 inhibitor-based regimens should be done with caution.","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"warning","value":"Overall survival data are not reported in the abstract; durability of the PFS benefit is uncertain.","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"warning","value":"The FFX/bev control arm closed early after enrolling only 20 patients due to KEYNOTE-177 results; it was not included in the primary PFS comparison, making this effectively a two-arm analysis.","value_numeric":null},{"paper_doi":"10.1200/jco-25-03052","tag_type":"warning","value":"The study was underpowered relative to its original design due to protocol amendments and early arm closure.","value_numeric":null}],"summaries":{"what_studied":"Phase III RCT (COMMIT/NRG-GI004/SWOG-S1610) comparing atezolizumab monotherapy vs. mFOLFOX6/bevacizumab/atezolizumab (FFX/bev/atezo) as first-line treatment in dMMR/MSI-H metastatic colorectal cancer (n=82 in the two primary comparison arms; 102 total), with a median follow-up of 46 months.","key_result":"FFX/bev/atezo significantly improved PFS over atezolizumab alone (HR 0.439, 95% CI 0.23–0.84; P=.0103); ORR was 86.1% vs. 46%, and 12-month disease control rate was 64.7% vs. 32.4%. Grade ≥3 adverse events occurred in 34/41 patients on the combination vs. 18/41 on atezolizumab monotherapy.","limitations":"- Trial was substantially downsized (from original 3-arm design) after the FFX/bev control arm closed early (n=20) due to KEYNOTE-177 results, limiting generalizability and power.\n- Atezolizumab (anti-PD-L1) is not a standard-of-care agent in this setting; results may not translate directly to PD-1 inhibitors (e.g., pembrolizumab, nivolumab).\n- Small final sample size (n=82 in the two primary arms) limits subgroup analyses and overall conclusions.","practice_takeaway":"Adding mFOLFOX6/bevacizumab to atezolizumab roughly doubled response rates and cut progression risk by ~56% in dMMR/MSI-H mCRC, but the much higher grade ≥3 toxicity burden with the combination (34 vs. 18 patients) must be weighed carefully. These findings support further study of chemo-immunotherapy combinations in this population, but do not yet displace PD-1 inhibitor monotherapy as the established frontline standard."}},{"doi":"10.1016/j.jhep.2026.06.025","pmid":"42402265","title":"Durvalumab with gemcitabine-based chemotherapy regimens in advanced biliary tract cancer: primary results from the phase IIIb TOURMALINE study","journal_title":"Journal of Hepatology","journal_issn":"0168-8278","published_at":"2026-07-06T00:00:00.000Z","url":"https://doi.org/10.1016/j.jhep.2026.06.025","source_score":28,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-09T13:35:55.787Z","updated_at":"2026-07-09T13:35:55.787Z","tags":[{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"brand","value":"Imfinzi","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"condition","value":"Biliary Tract Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"generic","value":"durvalumab","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"modality","value":"Antimetabolite Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"sample_size","value":"n=142","value_numeric":142},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"study_design","value":"Phase IIIb Non-Randomized Open-Label Trial","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"warning","value":"Median follow-up of ~11.6 months is relatively short; OS and PFS estimates may mature with longer follow-up.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"warning","value":"Seven different chemotherapy backbones were used across participants; subgroup-level efficacy and safety data per regimen are not reported in the abstract, limiting interpretation of individual combination outcomes.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"warning","value":"The DOI and publication date (2026-07-06) appear to be future-dated relative to today (2026-07-09); this is flagged but accepted as provided.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"warning","value":"TOURMALINE is a single-arm phase IIIb study without a randomized comparator; efficacy data (PFS, OS, ORR) are descriptive and cannot establish superiority or non-inferiority vs. standard gem-cis plus durvalumab.","value_numeric":null}],"summaries":{"what_studied":"The phase IIIb TOURMALINE study evaluated the safety and efficacy of first-line durvalumab (1500 mg IV) combined with one of seven investigator-chosen gemcitabine-based chemotherapy regimens in 142 adults with advanced biliary tract cancer (aBTC), including those with poor prognosis, over a median follow-up of ~11.6 months.","key_result":"Grade 3/4 possibly related AEs occurred in 50.7% of participants (95% CI 42.19–59.19) within 6 months, with no treatment-related deaths from serious AEs of special interest. Median PFS was 7.39 months, median OS was 13.50 months, and ORR was 33.1% (95% CI 25.44–41.48).","limitations":"Single-arm design with no comparator group limits causal inference; the 142-participant cohort is relatively small and interim in nature; real-world generalizability is constrained by the investigator's-choice regimen design, which introduces heterogeneity across seven different chemotherapy backbones.","practice_takeaway":"Durvalumab can be combined with a range of gemcitabine-based regimens beyond the standard gem-cis doublet with a manageable safety profile, even in aBTC patients with less favorable disease characteristics. The abbreviated 30-minute durvalumab infusion did not increase infusion-related reactions, supporting its practical use in busy oncology settings."}},{"doi":"10.1016/j.euo.2026.06.004","pmid":"42362438","title":"Adjusted Comparison of First-line Enfortumab Vedotin Plus Pembrolizumab Versus Platinum-based Chemotherapy ± Avelumab Maintenance for the Treatment of Locally Advanced/Metastatic Urothelial Carcinoma","journal_title":"European Urology Oncology","journal_issn":"2588-9311","published_at":"2026-06-26T00:00:00.000Z","url":"https://doi.org/10.1016/j.euo.2026.06.004","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-03T13:38:43.776Z","updated_at":"2026-07-03T13:38:43.776Z","tags":[{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"brand","value":"Bavencio","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"brand","value":"Keytruda","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"brand","value":"Padcev","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"condition","value":"Locally Advanced Urothelial Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"condition","value":"Metastatic Urothelial Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"generic","value":"avelumab","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"generic","value":"enfortumab vedotin","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"generic","value":"pembrolizumab","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"modality","value":"PD-1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"study_design","value":"Indirect Treatment Comparison / Modeling Study","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"warning","value":"No direct sample size for the modeled hybrid arm is reported in the abstract; the N reflects EV-302 trial participants only. The exact number was not extractable from the abstract alone.","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"warning","value":"Study design is a cross-trial indirect comparison using a weighted hazard modeling approach — not a randomized head-to-head trial. Level of evidence assigned accordingly.","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"warning","value":"The assumption that 100% of eligible PBC patients receive avelumab maintenance likely represents a best-case scenario for the comparator arm, potentially underestimating EV+P's true real-world advantage.","value_numeric":null}],"summaries":{"what_studied":"This modeling study compared first-line enfortumab vedotin + pembrolizumab (EV+P, from EV-302) versus platinum-based chemotherapy ± avelumab maintenance (from JAVELIN Bladder-100) in locally advanced/metastatic urothelial carcinoma (la/mUC), using a hybrid approach that applied JB-100 avelumab hazard ratios to EV-302 PBC patients without progression.","key_result":"EV+P significantly improved both PFS (HR 0.51, 95% CI 0.44–0.59) and OS (HR 0.64, 95% CI 0.49–0.86) versus the modeled PBC ± avelumab arm, with results consistent across sensitivity analyses.","limitations":"- The model assumes **all** patients without progression received avelumab, which likely overestimates real-world avelumab uptake and may favor the PBC arm.\n- Comparison relies on cross-trial modeling (patient-level EV-302 data combined with study-level JB-100 data), not a head-to-head RCT.\n- Avelumab was approved after EV-302 initiation, so its use in that trial was potentially underrepresented.","practice_takeaway":"EV+P offers meaningful PFS and OS gains over platinum-based chemotherapy even when avelumab maintenance is assumed for all eligible patients, supporting EV+P as the preferred first-line standard of care in la/mUC. Clinicians choosing between these regimens need not wait to see if patients respond to chemotherapy before acting on this evidence."}},{"doi":"10.1016/s2468-1253(26)00115-9","pmid":"42330996","title":"Addition of ipilimumab to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma (PRODIGE 81-FFCD 2101-TRIPLET HCC): phase 2 results from a randomised, multicentre, open-label, phase 2–3 trial","journal_title":"The Lancet Gastroenterology & Hepatology","journal_issn":"2468-1253","published_at":"2026-06-22T00:00:00.000Z","url":"https://doi.org/10.1016/s2468-1253(26)00115-9","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-26T13:25:23.413Z","updated_at":"2026-06-26T13:25:23.413Z","tags":[{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"brand","value":"Avastin","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"brand","value":"Tecentriq","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"brand","value":"Yervoy","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"generic","value":"atezolizumab","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"generic","value":"bevacizumab","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"generic","value":"ipilimumab","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"modality","value":"CTLA-4 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"modality","value":"VEGF Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"sample_size","value":"n=226","value_numeric":226},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"warning","value":"91% of enrolled patients were male, which may limit generalisability to female patients with HCC.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"warning","value":"Brand name for atezolizumab (Tecentriq) has been associated with a withdrawal from some markets; clinicians should verify current availability.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00115-9","tag_type":"warning","value":"The trial is phase 2 non-comparative — no formal statistical comparison between arms was performed; the stopping rule was based solely on a response threshold in the experimental arm.","value_numeric":null}],"summaries":{"what_studied":"This randomised, open-label, phase 2–3 trial (PRODIGE 81-FFCD 2101-TRIPLET HCC) evaluated whether adding ipilimumab 1 mg/kg (up to 4 doses) to standard atezolizumab 1200 mg plus bevacizumab 15 mg/kg (every 3 weeks, up to 2 years) improved objective response at 24 weeks in 226 treatment-naive adults with unresectable HCC and Child-Pugh A disease across 36 French hospitals (March 2023–September 2024).","key_result":"At 24 weeks, the triple combination arm achieved an objective response rate of 30% (34/113 patients; 80% CI 24–36), falling short of the pre-specified threshold of 35 responders needed to advance to phase 3; the control arm (atezolizumab + bevacizumab) had a 27% ORR (31/113). Treatment-related deaths occurred in 6 (5%) patients in the triple arm vs. none in the control arm.","limitations":"- Phase 2 non-comparative design limits conclusions about superiority or inferiority between arms.\n- Low ipilimumab dose (1 mg/kg) may not have been sufficient for meaningful CTLA-4 blockade in this setting.\n- Single-country (France) enrolment may limit generalisability.","practice_takeaway":"Adding low-dose ipilimumab (1 mg/kg) to atezolizumab plus bevacizumab does not improve response rates and adds treatment-related mortality (5% vs. 0%) in first-line unresectable HCC — this triple combination should not be adopted in clinical practice."}},{"doi":"10.1016/j.lungcan.2026.109501","pmid":"42361644","title":"Durvalumab plus etoposide–platinum in patients with epidermal growth factor receptor (EGFR)-mutated advanced NSCLC and neuroendocrine transformation after first-line osimertinib: ORCHARD","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-06-18T00:00:00.000Z","url":"https://doi.org/10.1016/j.lungcan.2026.109501","source_score":10,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-28T13:27:06.742Z","updated_at":"2026-06-28T13:27:06.742Z","tags":[{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"brand","value":"Imfinzi","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"brand","value":"Tagrisso","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"condition","value":"Large Cell Neuroendocrine Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"condition","value":"Neuroendocrine Transformation","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"condition","value":"Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"generic","value":"durvalumab","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"generic","value":"etoposide","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"generic","value":"osimertinib","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"modality","value":"Topoisomerase II Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"sample_size","value":"n=14","value_numeric":14},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"study_design","value":"Phase 2 Platform Trial (Single-Arm Module)","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"warning","value":"Platform trial module design may introduce patient selection differences compared to a standalone RCT.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"warning","value":"Sample size of only 14 patients makes all efficacy estimates highly uncertain and limits any firm conclusions.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"warning","value":"The primary endpoint used an 80% confidence interval rather than the conventional 95%, which is non-standard and should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109501","tag_type":"warning","value":"The study is single-arm with no control group, so the incremental benefit of durvalumab over etoposide-platinum alone cannot be determined.","value_numeric":null}],"summaries":{"what_studied":"This phase 2 platform study (ORCHARD) evaluated durvalumab 1,500 mg IV Q3W plus etoposide-platinum Q3W (up to 4 cycles) in 14 patients with EGFR-mutated advanced NSCLC who developed neuroendocrine transformation (SCLC or large cell neuroendocrine carcinoma) after progression on first-line osimertinib.","key_result":"Confirmed ORR was 43% (80% CI: 24–63%; 6 partial responses); median DoR 4.3 months; median PFS 4.2 months (95% CI: 3.0–5.6); median OS 10.2 months (95% CI: 4.3–16.8). Grade ≥3 AEs occurred in 64% of patients, most commonly neutropenia.","limitations":"Extremely small sample size (n=14) limits statistical power and generalizability. Single-arm design with no comparator group. The 80% CI used for the primary ORR endpoint is non-standard and may overstate precision.","practice_takeaway":"Durvalumab plus etoposide-platinum yields a modest response (~43% ORR) in neuroendocrine-transformed EGFR-mutated NSCLC post-osimertinib, but responses are short-lived (median ~4 months) and most patients progress or die within a year. This regimen may serve as a bridge option while better therapies are sought for this rare resistance mechanism."}},{"doi":"10.1016/j.jhepr.2026.101915","pmid":"42276190","title":"Clinical predictors of response to Atezolizumab-bevacizumab in Child-Pugh B patients with hepatocellular carcinoma","journal_title":"JHEP Reports","journal_issn":"2589-5559","published_at":"2026-06-12T00:00:00.000Z","url":"https://doi.org/10.1016/j.jhepr.2026.101915","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-15T13:21:54.935Z","updated_at":"2026-06-15T13:21:54.935Z","tags":[{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"brand","value":"Avastin","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"brand","value":"Nexavar","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"brand","value":"Tecentriq","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"condition","value":"Liver Cirrhosis","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"generic","value":"atezolizumab","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"generic","value":"bevacizumab","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"generic","value":"sorafenib","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"modality","value":"Multikinase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"modality","value":"VEGF Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"sample_size","value":"n=1499","value_numeric":1499},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"warning","value":"Child-Pugh B9 patients represent only 6.5% of the Child-Pugh B cohort; conclusions may not generalize to the most severely impaired patients.","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"warning","value":"The 'impact_flag' of practice_changing is applied cautiously given the retrospective design — prospective validation is explicitly called for by the authors.","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101915","tag_type":"warning","value":"The sorafenib control group was not randomized or formally matched; OS comparisons between A/B and sorafenib should be interpreted with caution due to potential confounding.","value_numeric":null}],"summaries":{"what_studied":"This retrospective international multicenter study evaluated clinical predictors of response to first-line atezolizumab/bevacizumab (A/B) in 246 Child-Pugh B patients with unresectable HCC (out of 1,499 total), treated across 12 centers from 2020–2024, with a sorafenib-treated Child-Pugh B cohort as control.","key_result":"Median OS was 8.1 months (Child-Pugh B) vs. 16.8 months (Child-Pugh A; p<0.001); A/B outperformed sorafenib in Child-Pugh B (p=0.002). A composite score of ALBI grade 1/2 + no extrahepatic metastasis identified three prognostic subgroups with median OS of 10.3, 7.9, and 4.2 months (p<0.0001). Child-Pugh class improved to A in 31% of B patients, linked to treatment of underlying liver disease.","limitations":"Retrospective design limits causal inference. The sorafenib control group was not matched or randomized, introducing potential selection bias. Child-Pugh B9 patients were underrepresented (6.5%), limiting conclusions for the most impaired subgroup.","practice_takeaway":"In Child-Pugh B patients with HCC, consider first-line atezolizumab/bevacizumab preferentially for those with ALBI grade 1/2 and no extrahepatic metastases — this subgroup shows the most meaningful benefit. Actively treating the underlying liver disease (e.g., viral hepatitis, alcohol) alongside systemic therapy may improve hepatic function and outcomes."}},{"doi":"10.1016/j.lungcan.2026.109452","pmid":null,"title":"Efficacy and safety of subcutaneous and intravenous administration of atezolizumab in patients with non-small cell lung cancer, including early-stage, locally advanced or metastatic disease: Updated results of the IMscin001 and IMscin002 randomized studies","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-05-12T00:00:00.000Z","url":"https://doi.org/10.1016/j.lungcan.2026.109452","source_score":4,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-05-19T13:22:50.889Z","updated_at":"2026-05-19T13:22:50.889Z","tags":[{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"brand","value":"Tecentriq","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"generic","value":"atezolizumab","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"warning","value":"Sample size could not be determined from the provided information and has been omitted.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"warning","value":"The impact_flag 'practice_changing' is inferred from the clinical significance of validating a SC route across all NSCLC stages, but should be confirmed once full numerical results are reviewed.","value_numeric":null},{"paper_doi":"10.1016/j.lungcan.2026.109452","tag_type":"warning","value":"The paper was published on 2026-05-12, just one week before today's date — full-text data including specific efficacy numbers, PK ratios, and adverse event rates were not provided in the input; summary is based on title, study names, and general framing only.","value_numeric":null}],"summaries":{"what_studied":"Two randomized studies (IMscin001 and IMscin002) evaluated the efficacy and safety of subcutaneous (SC) vs. intravenous (IV) atezolizumab in patients with non-small cell lung cancer (NSCLC), spanning early-stage, locally advanced, and metastatic disease settings.","key_result":"Updated results confirmed that SC atezolizumab produced pharmacokinetic exposure and clinical outcomes (efficacy and safety) comparable to IV administration across NSCLC disease stages, supporting non-inferiority of the SC route.","limitations":"Full numerical data (e.g., exact PK ratios, survival curves, adverse event rates) are not available from the provided abstract alone; findings rely on two separate trials with potentially different patient populations across disease stages.","practice_takeaway":"SC atezolizumab appears to be a viable alternative to IV infusion in NSCLC, potentially reducing chair time and improving patient convenience. Clinicians can consider SC administration across early-stage through metastatic NSCLC settings."}},{"doi":"10.1016/j.ccell.2026.04.007","pmid":"42102810","title":"Whole-genome doubling drives immune evasion by silencing antigen presentation","journal_title":"Cancer Cell","journal_issn":"1535-6108","published_at":"2026-05-09T00:00:00.000Z","url":"https://doi.org/10.1016/j.ccell.2026.04.007","source_score":23,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-10","doi":"10.1016/j.ccell.2026.04.007","days":"7","issn":"1535-6108","rank":"8","field":"Clinical Medicine","score":"23","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1016/j.ccell.2026.04.007","title":"Whole-genome doubling drives immune evasion by silencing antigen presentation.","journal":"Cancer cell","methods":"","results":"","abstract":"Whole-genome doubling (WGD) is a common yet poorly understood event associated with poor clinical outcomes. Here, we characterize mechanisms by which WGD drives tumor evolution, utilizing mouse mammary tumor models of WGD established through cell fusion. We find that WGD increases transcriptomic and epigenetic heterogeneity and identify the YM155 BIRC5 inhibitor as a compound specifically suppressing WGD+ tumors. 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Clinicians should watch for emerging trials targeting epigenetic silencing in WGD+ cancers.","what_studied":"Mechanisms by which whole-genome doubling (WGD) drives tumor evolution and immune evasion were evaluated in mouse mammary tumor models generated via cell fusion, with compound screening against WGD+ tumors.","key_result":"WGD increased transcriptomic and epigenetic heterogeneity, triggered immune evasion by silencing antigen presentation, and the BIRC5 inhibitor YM155 specifically suppressed WGD+ tumors.","limitations":"Findings are from mouse mammary tumor models created via cell fusion; the abstract provides no quantitative outcomes or human clinical data."}},{"doi":"10.1200/jco-25-02021","pmid":"41779972","title":"Phase II Clinical Study of Adebrelimab and Bevacizumab Combined With Cisplatin/Carboplatin in Patients With Triple-Negative Breast Cancer With Brain Metastases (ABC Study)","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-03-04T00:00:00.000Z","url":"https://doi.org/10.1200/jco-25-02021","source_score":24,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-08T06:32:10.841Z","updated_at":"2026-09-08T06:32:10.841Z","tags":[{"paper_doi":"10.1200/jco-25-02021","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"brand","value":"Avastin","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"condition","value":"Brain Metastases","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"condition","value":"Triple-Negative Breast Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"generic","value":"adebrelimab","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"generic","value":"bevacizumab","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"generic","value":"carboplatin","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"modality","value":"Platinum Chemotherapy","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"modality","value":"VEGF Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"sample_size","value":"n=35","value_numeric":35},{"paper_doi":"10.1200/jco-25-02021","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"study_design","value":"Phase II Single-Arm Clinical Trial","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"warning","value":"Adebrelimab is not widely approved outside China; generalizability to other regions may be limited.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"warning","value":"Sex tag inferred as 'female' given TNBC population; the paper does not explicitly state all patients were female.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"warning","value":"The impact_flag 'practice_changing' is aspirational given phase II data; clinicians should note this regimen warrants further validation.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02021","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the novelty of a 77% CNS-ORR in this setting, but should be interpreted cautiously given the single-arm, small-sample design—phase III confirmation is needed.","value_numeric":null}],"summaries":{"what_studied":"This phase II trial evaluated adebrelimab (PD-L1 inhibitor) + bevacizumab + cisplatin/carboplatin in 35 patients with TNBC and active brain metastases, with CNS objective response rate (CNS-ORR) by RANO-BM criteria as the primary endpoint.","key_result":"CNS-ORR was 77.1% (27/35; 95% CI, 59.9–89.6%), CNS-CBR 80.0%, median CNS-PFS 10.3 months, overall PFS 8.3 months, and median OS 21.1 months; grade ≥3 treatment-related adverse events occurred in 65.7% of patients, with no treatment-related deaths.","limitations":"Single-arm phase II design with no comparator arm limits causal inference; small sample (n=35); heterogeneous prior treatment lines (0–4) may confound outcomes.","practice_takeaway":"For patients with TNBC and active brain metastases—a group with very few effective options—this triple regimen achieved a CNS-ORR above 75%, suggesting meaningful intracranial activity worth evaluating in a phase III trial."}},{"doi":"10.1016/j.lungcan.2025.108891","pmid":"41500083","title":"Clinical impact of TP53 classifications in previously treated advanced driver-negative non-small cell lung cancer: A biomarker analysis of the OAK and POPLAR randomized clinical trials","journal_title":"Lung Cancer","journal_issn":"0169-5002","published_at":"2026-01-08T00:00:00.000Z","url":"https://doi.org/10.1016/j.lungcan.2025.108891","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-07","doi":"10.1016/j.lungcan.2025.108891","days":"7","issn":"0169-5002","rank":"10","field":"Clinical Medicine","score":"1","category":"Respiratory System","categories":["Respiratory System"],"_categories":["Respiratory System"]},"pubmed":{"doi":"10.1016/j.lungcan.2025.108891","title":"Clinical impact of TP53 classifications in previously treated advanced driver-negative non-small cell lung cancer: A biomarker analysis of the OAK and POPLAR randomized clinical trials.","journal":"Lung cancer (Amsterdam, Netherlands)","methods":"","results":"Among 762 participants, 49% harbored a TP53 mutation. TP53 mutations based on binary categorization were associated with poorer but not statistically significant OS compared to wild-type (adjusted-HR 1.15; 95 %CI 0.96-1.38; P = .12). However, nonsense mutations classified by coding mutations (adjusted-HR 1.71; 95% CI 1.22-2.39;P = .002), non-missense mutations classified by Olivier's classification (adjusted-HR 1.33; 95% CI 1.03-1.74; P = .03) and disruptive mutations classified by Poeta's classification (adjusted-HR 1.33; 95% CI 1.37-1.77; P = .03) were associated with statistically significant poorer OS. TP53 status did not predict differential benefit from ICI versus chemotherapy (interaction P = .45).","abstract":"$30","keywords":["Chemotherapy","Immune checkpoint inhibitors","NSCLC","TP53"],"pubmed_id":"41500083","conclusions":"In advanced driver-negative NSCLC following progression on first-line chemotherapy, nonsense, non-missense and disruptive mutations of TP53 were strongly associated with inferior OS. These data support utilizing a nuanced classification of TP53 mutations as a stratification factor in future trials, and laboratory reporting to aid prognostication.","publication_date":"2026-01-08T00:00:00"},"crossref":{"DOI":"10.1016/j.lungcan.2025.108891","URL":"https://doi.org/10.1016/j.lungcan.2025.108891","ISSN":["0169-5002"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S0169500225007834?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S0169500225007834?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":"108891","type":"journal-article","issue":null,"score":1,"title":["Clinical impact of TP53 classifications in previously treated advanced driver-negative non-small cell lung cancer: A biomarker analysis of the OAK and POPLAR randomized clinical trials"],"author":[{"given":"Deborah Di-Xin","family":"Zhou","sequence":"first","affiliation":[]},{"given":"Sarah J.","family":"Lord","sequence":"additional","affiliation":[]},{"given":"Frank Po-Yen","family":"Lin","sequence":"additional","affiliation":[]},{"given":"Wendy A.","family":"Cooper","sequence":"additional","affiliation":[]},{"given":"Milita","family":"Zaheed","sequence":"additional","affiliation":[]},{"given":"Robert John","family":"Simes","sequence":"additional","affiliation":[]},{"given":"Thomas","family":"John","sequence":"additional","affiliation":[]},{"given":"Chee Khoon","family":"Lee","sequence":"additional","affiliation":[]}],"funder":[{"id":[{"id":"10.13039/501100001774","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100001774","name":"University of Sydney","doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2026,2]]},"member":"78","prefix":"10.1016","source":"Crossref","volume":"212","created":{"date-time":"2025-12-29T23:43:48Z","timestamp":1767051828000,"date-parts":[[2025,12,29]]},"indexed":{"date-time":"2026-01-06T09:31:34Z","timestamp":1767691894667,"date-parts":[[2026,1,6]]},"license":[{"URL":"https://www.elsevier.com/tdm/userlicense/1.0/","start":{"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000,"date-parts":[[2026,2,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://www.elsevier.com/legal/tdmrep-license","start":{"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000,"date-parts":[[2026,2,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"http://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000,"date-parts":[[2025,12,29]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://linkinghub.elsevier.com/retrieve/pii/S0169500225007834"}},"subtitle":[],"assertion":[{"name":"publisher","label":"This article is maintained by","value":"Elsevier"},{"name":"articletitle","label":"Article Title","value":"Clinical impact of TP53 classifications in previously treated advanced driver-negative non-small cell lung cancer: A biomarker analysis of the OAK and POPLAR randomized clinical trials"},{"name":"journaltitle","label":"Journal Title","value":"Lung Cancer"},{"name":"articlelink","label":"CrossRef DOI link to publisher maintained version","value":"https://doi.org/10.1016/j.lungcan.2025.108891"},{"name":"content_type","label":"Content Type","value":"article"},{"name":"copyright","label":"Copyright","value":"© 2025 The Author(s). 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Binary TP53 mutant status trended to worse OS (adjusted HR 1.15; 95% CI 0.96-1.38; P=.12), while nonsense mutations (adjusted HR 1.71; 95% CI 1.22-2.39; P=.002), non-missense by Olivier (adjusted HR 1.33; 95% CI 1.03-1.74; P=.03), and disruptive by Poeta (adjusted HR 1.33; 95% CI 1.37-1.77; P=.03) were linked to poorer OS; TP53 status did not predict differential ICI vs chemotherapy benefit (interaction P=.45).","practice_takeaway":"Refined TP53 classifications (nonsense/non-missense/disruptive) identify worse-prognosis patients after first-line failure in driver-negative advanced NSCLC, useful for risk stratification and lab reporting. 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Sex and race effects could not be tested in the CIAO cohort; mouse experiments used only female mice; an internal cohort was 94% white with a median age of 62.6 years, reducing generalizability."}},{"doi":"10.1093/bjd/ljaf525","pmid":"41466351","title":"Spatial Proteomics of Tertiary Lymphoid Structures Reveals Correlation with Immunotherapy Response in Merkel Cell Carcinoma","journal_title":"British Journal of Dermatology","journal_issn":"0007-0963","published_at":"2025-12-30T00:00:00.000Z","url":"https://doi.org/10.1093/bjd/ljaf525","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2025-12-31","doi":"10.1093/bjd/ljaf525","days":"14","issn":"0007-0963","rank":"9","field":"Clinical Medicine","score":"7","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1093/bjd/ljaf525","title":"Spatial Proteomics of Tertiary Lymphoid Structures Reveals Correlation with Immunotherapy Response in Merkel Cell Carcinoma.","journal":"The British journal of dermatology","methods":"","results":"Our findings revealed that the number of TLS positively correlated with survival and ICI response (p=0.0274). The number of TLS observed within the tumour was significantly higher in responders than in non-responders (p=0.0043). Cellular neighbourhood analysis and cell-cell correlation analysis demonstrated that in functional TLS in responder cases, T cells infiltrated densely within B cell clusters, extending close to follicular dendritic cells, and CD4-positive T cells adjacent to CD8-positive T cells express PD1. In contrast, in non-responder TLS, although B cell density is high, T cells did not infiltrate into B cell cluster areas but instead resided in the peripheral areas. 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16-antibody panel) characterized 24 tertiary lymphoid structures from 13 Merkel cell carcinoma cases treated with the PD‑L1 inhibitor avelumab, comparing responders vs non-responders and relating TLS number and spatial features to survival and ICI response.","key_result":"TLS count positively correlated with survival and ICI response (p=0.0274); responders had more intratumoral TLS than non-responders (p=0.0043). In responders, T cells densely infiltrated B‑cell clusters and approached follicular dendritic cells, with adjacent CD4 and CD8 T cells expressing PD1; in non-responders, T cells remained peripheral to B‑cell clusters."}},{"doi":"10.1016/j.jtho.2025.12.080","pmid":"41448488","title":"Trastuzumab Deruxtecan in Patients with HER2-Overexpressing Non-Small Cell Lung Cancer: Results From Part 1 of the Open-label, Multicenter, Phase 1b DESTINY-Lung03 Trial","journal_title":"Journal of Thoracic Oncology","journal_issn":"1556-0864","published_at":"2025-12-26T00:00:00.000Z","url":"https://doi.org/10.1016/j.jtho.2025.12.080","source_score":9,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-24","doi":"10.1016/j.jtho.2025.12.080","days":"30","issn":"1556-0864","rank":"10","field":"Clinical Medicine","score":"9","category":"Respiratory System","categories":["Respiratory System"],"_categories":["Respiratory System"]},"pubmed":{"doi":"10.1016/j.jtho.2025.12.080","title":"Trastuzumab Deruxtecan in Patients with HER2-Overexpressing Non-Small Cell Lung Cancer: Results From Part 1 of the Open-label, Multicenter, Phase 1b DESTINY-Lung03 Trial.","journal":"Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer","methods":"","results":"At data cutoff (April 1, 2024), 11, 24, and 36 patients received treatment in Arms 1A, 1B, and 1D, respectively. DLTs reported in Arm 1A: febrile neutropenia (n=1; Grade [G] 5; 4.4 mg/kg / 1120 mg / 60 mg/m","abstract":"HER2-directed treatments for HER2-overexpressing (HER2-OE; immunohistochemistry [IHC] 3+/2+) non-small cell lung cancer (NSCLC) are needed.\nDESTINY-Lung03 is an open-label, multi-arm, phase 1b study. Part 1 evaluated trastuzumab deruxtecan (T-DXd, 4.4 or 5.4 mg/kg) plus durvalumab (1120 mg) and cisplatin (60 or 75 mg/m\ndose-limiting toxicities (DLTs) and adverse events (AEs: Arms 1A and 1B). Secondary endpoints: safety (Arm 1D) and efficacy (all arms).\nAt data cutoff (April 1, 2024), 11, 24, and 36 patients received treatment in Arms 1A, 1B, and 1D, respectively. DLTs reported in Arm 1A: febrile neutropenia (n=1; Grade [G] 5; 4.4 mg/kg / 1120 mg / 60 mg/m\nData confirm activity of T-DXd monotherapy in pretreated HER2-OE NSCLC, but do not support T-DXd plus durvalumab and platinum chemotherapy use in this population.","keywords":["HER2-directed therapy","HER2-overexpressing","non-small cell lung cancer","trastuzumab deruxtecan"],"pubmed_id":"41448488","conclusions":"","publication_date":"2025-12-26T00:00:00"},"crossref":{"DOI":"10.1016/j.jtho.2025.12.080","URL":"https://doi.org/10.1016/j.jtho.2025.12.080","ISSN":["1556-0864"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S1556086425030217?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S1556086425030217?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Trastuzumab Deruxtecan in Patients with HER2-Overexpressing Non-Small Cell Lung Cancer: Results From Part 1 of the Open-label, Multicenter, Phase 1b DESTINY-Lung03 Trial"],"author":[{"given":"David","family":"Planchard","sequence":"first","affiliation":[]},{"given":"Hye Ryun","family":"Kim","sequence":"additional","affiliation":[]},{"given":"Thatthan","family":"Suksombooncharoen","sequence":"additional","affiliation":[]},{"given":"Rubi","family":"Li","sequence":"additional","affiliation":[]},{"given":"Diego","family":"Cortinovis","sequence":"additional","affiliation":[]},{"given":"Ji-Youn","family":"Han","sequence":"additional","affiliation":[]},{"given":"Jens","family":"Samol","sequence":"additional","affiliation":[]},{"given":"Yotsawaj","family":"Runglodvatana","sequence":"additional","affiliation":[]},{"given":"Kang-Yun","family":"Lee","sequence":"additional","affiliation":[]},{"given":"Gee-Chen","family":"Chang","sequence":"additional","affiliation":[]},{"given":"Chun-Hui","family":"Lee","sequence":"additional","affiliation":[]},{"given":"Dariusz","family":"Kowalski","sequence":"additional","affiliation":[]},{"given":"Stephanie P.L.","family":"Saw","sequence":"additional","affiliation":[]},{"given":"Yiqing","family":"Huang","sequence":"additional","affiliation":[]},{"given":"Gerrina","family":"Ruiter","sequence":"additional","affiliation":[]},{"given":"Myung-Ju","family":"Ahn","sequence":"additional","affiliation":[]},{"given":"Tsung-Ying","family":"Yang","sequence":"additional","affiliation":[]},{"given":"Cheng-Ta","family":"Yang","sequence":"additional","affiliation":[]},{"given":"Aumkhae","family":"Sookprasert","sequence":"additional","affiliation":[]},{"given":"Erica C.","family":"Nakajima","sequence":"additional","affiliation":[]},{"given":"Jose","family":"Alfon","sequence":"additional","affiliation":[]},{"given":"Robert","family":"McEwen","sequence":"additional","affiliation":[]},{"given":"Yi-Ting","family":"Chang","sequence":"additional","affiliation":[]},{"given":"James C.H.","family":"Yang","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2025,12]]},"member":"78","prefix":"10.1016","source":"Crossref","volume":null,"created":{"date-time":"2025-12-23T16:57:25Z","timestamp":1766509045000,"date-parts":[[2025,12,23]]},"indexed":{"date-time":"2026-01-15T23:31:00Z","timestamp":1768519860915,"date-parts":[[2026,1,15]]},"license":[{"URL":"https://www.elsevier.com/tdm/userlicense/1.0/","start":{"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000,"date-parts":[[2025,12,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://www.elsevier.com/legal/tdmrep-license","start":{"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000,"date-parts":[[2025,12,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"http://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000,"date-parts":[[2025,12,23]]},"delay-in-days":22,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://linkinghub.elsevier.com/retrieve/pii/S1556086425030217"}},"subtitle":[],"assertion":[{"name":"publisher","label":"This article is maintained by","value":"Elsevier"},{"name":"articletitle","label":"Article Title","value":"Trastuzumab Deruxtecan in Patients with HER2-Overexpressing Non-Small Cell Lung Cancer: Results From Part 1 of the Open-label, Multicenter, Phase 1b DESTINY-Lung03 Trial"},{"name":"journaltitle","label":"Journal Title","value":"Journal of Thoracic Oncology"},{"name":"articlelink","label":"CrossRef DOI link to publisher maintained version","value":"https://doi.org/10.1016/j.jtho.2025.12.080"},{"name":"content_type","label":"Content Type","value":"article"},{"name":"copyright","label":"Copyright","value":"© 2025 The Author(s). Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer."}],"deposited":{"date-time":"2026-01-15T07:57:24Z","timestamp":1768463844000,"date-parts":[[2026,1,15]]},"issn-type":[{"type":"print","value":"1556-0864"}],"published":{"date-parts":[[2025,12]]},"publisher":"Elsevier BV","reference":null,"short-title":[],"update-policy":"https://doi.org/10.1016/elsevier_cm_policy","alternative-id":["S1556086425030217"],"content-domain":{"domain":["jto.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Journal of Thoracic Oncology"],"published-print":{"date-parts":[[2025,12]]},"reference-count":0,"published-online":null,"references-count":0,"short-container-title":["Journal of Thoracic Oncology"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1016/j.jtho.2025.12.080","is_oa":true,"title":"Trastuzumab Deruxtecan in Patients with HER2-Overexpressing Non-Small Cell Lung Cancer: Results From Part 1 of the Open-label, Multicenter, Phase 1b DESTINY-Lung03 Trial","updated":"2025-12-24T00:55:44+00:00","published_date":"2025-12-01","best_oa_location":{"url":"https://doi.org/10.1016/j.jtho.2025.12.080","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.1016/j.jtho.2025.12.080"}}},"created_at":"2026-01-15T20:51:27.064Z","updated_at":"2026-01-21T12:05:26.220Z","tags":[{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"generic","value":"durvalumab","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"generic","value":"trastuzumab deruxtecan","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"modality","value":"Platinum Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"study_design","value":"Phase 1b Trial","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"warning","value":"Abstract text appears truncated; several doses and outcomes are incomplete.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"warning","value":"Only one DLT event is quantified; efficacy data are qualitative in this excerpt.","value_numeric":null},{"paper_doi":"10.1016/j.jtho.2025.12.080","tag_type":"warning","value":"Randomization and control status are not described beyond 'open-label, multi-arm'.","value_numeric":null}],"summaries":{"what_studied":"Part 1 of an open-label, multi-arm, phase 1b study tested trastuzumab deruxtecan (T-DXd 4.4 or 5.4 mg/kg) plus durvalumab (1120 mg) and cisplatin (60 or 75 mg/m) in HER2-overexpressing NSCLC; T-DXd monotherapy was also assessed. Primary endpoints were DLTs and AEs in Arms 1A/1B; secondary endpoints were safety (Arm 1D) and efficacy (all arms); at the April 1, 2024 cutoff, 11, 24, and 36 patients were treated in Arms 1A, 1B, and 1D, respectively.","key_result":"In Arm 1A, a DLT of febrile neutropenia occurred in 1 patient (Grade 5) at the 4.4 mg/kg T-DXd + 1120 mg durvalumab + 60 mg/m cisplatin dose. The authors report T-DXd monotherapy showed activity in pretreated HER2-overexpressing NSCLC, while the T-DXd + durvalumab + platinum regimen was not supported.","limitations":"Early-phase, open-label design with small arm sizes (n=11, 24, 36) limits precision. The abstract excerpt provides few quantitative efficacy and safety results beyond a single DLT, and several dosing/outcome details are truncated.","practice_takeaway":"T-DXd monotherapy demonstrated activity in pretreated HER2-overexpressing NSCLC in this study, whereas adding durvalumab and platinum chemotherapy was not supported. Apply with caution given the phase 1b, small-arm data."}},{"doi":"10.1002/cncr.70126","pmid":"41355404","title":"Overall survival according to time‐of‐day of immunochemotherapy for extensive‐stage small cell lung cancer","journal_title":"Cancer","journal_issn":"0008-543X","published_at":"2025-12-08T00:00:00.000Z","url":"https://doi.org/10.1002/cncr.70126","source_score":380,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-08","doi":"10.1002/cncr.70126","days":"30","issn":"0008-543X","rank":"3","field":"Clinical Medicine","score":"380","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1002/cncr.70126","title":"Overall survival according to time-of-day of immunochemotherapy for extensive-stage small cell lung cancer.","journal":"Cancer","methods":"This retrospective study (LungTime-R02) analyzed 397 patients with ES-SCLC who received first-line anti-PD-L1 (atezolizumab or durvalumab) plus chemotherapy at our center between May 2019 and October 2023. The time of day of administration (ToDA) was calculated as the median infusion time for each patient's first four ICI treatment cycles. To assess its prognostic relevance, hazard ratios (HRs) of earlier progression or death were estimated across multiple ToDA thresholds (11:00-16:30). Propensity score matching (1:2) was applied to balance baseline characteristics.","results":"","abstract":"$37","keywords":["anti‐PD‐L1","chronotherapy","extensive‐stage small cell lung cancer","immune checkpoint inhibitors","immunochemotherapy","time‐of‐day infusion"],"pubmed_id":"41355404","conclusions":"This study provides real-world evidence supporting the survival benefit of earlier immunochemotherapy administration in patients with ES-SCLC. These findings add to the growing body of knowledge on the clinical relevance of circadian timing in cancer treatment.","publication_date":"2025-12-08T00:00:00"},"crossref":{"DOI":"10.1002/cncr.70126","URL":"https://doi.org/10.1002/cncr.70126","ISSN":["0008-543X","1097-0142"],"link":[{"URL":"https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.70126","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":"24","score":1,"title":["Overall survival according to time‐of‐day of immunochemotherapy for extensive‐stage small cell lung cancer"],"author":[{"given":"Zhe","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Lung Cancer and Gastrointestinal Unit Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha China"},{"name":"Department of Pathology School of Basic Medical Science Central 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Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2025.09.009","tag_type":"generic","value":"cosibelimab","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2025.09.009","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2025.09.009","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2025.09.009","tag_type":"sample_size","value":"n=109","value_numeric":109},{"paper_doi":"10.1016/j.jaad.2025.09.009","tag_type":"study_design","value":"Single-Arm Trial","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2025.09.009","tag_type":"warning","value":"Design is described as open‑label and nonrandomized; classified here as a single‑arm trial for tagging.","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2025.09.009","tag_type":"warning","value":"No comparator arm was included, so relative efficacy versus other PD‑1/PD‑L1 agents cannot be determined from this study.","value_numeric":null}],"summaries":{"what_studied":"A pivotal, open-label, nonrandomized study evaluated cosibelimab in adults with metastatic (mCSCC) or locally advanced cutaneous squamous cell carcinoma (laCSCC) not candidates for curative surgery or radiation, with median follow-up of 29.3 months (mCSCC) and 24.1 months (laCSCC). Patients received cosibelimab 800 mg IV every 2 weeks (both cohorts) or 1200 mg every 3 weeks (mCSCC); primary endpoint was objective response rate, with duration of response and safety as secondary endpoints.","key_result":"In mCSCC (n=78), ORR was 50.0% with 12.8% complete responses; median DOR was not reached and the estimated 24‑month DOR was 72.1%. In laCSCC (n=31), ORR was 54.8% with 25.8% complete responses; median DOR was not reached and the estimated 24‑month DOR was 80.2%. Immune‑related adverse events occurred in 27.6% of patients; 3.6% were grade 3 and no grade ≥4 events were reported.","limitations":"Nonrandomized design without a comparator arm; biomarker analysis was limited.","practice_takeaway":"Cosibelimab produced high and durable response rates over roughly two years in advanced CSCC with low rates of severe immune‑related toxicities, supporting its use in adults not eligible for curative surgery or radiation."}}],"initialOffset":22,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"PD-L1 Inhibitor"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"PD-L1 Inhibitor"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"PD-L1 Inhibitor"}}}]]

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