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:T4f0,A total of 139 participants were included in this analysis. ICGA-confirmed PCV was present in 44 participants in the treatment group receiving aflibercept, 8 mg, every 12 weeks (mean [SD] age, 72.2 [8.1] years; 50% male), 41 participants receiving 8 mg every 16 weeks (mean [SD] age, 73.2 [8.7] years; 63% male), and 54 participants receiving 2 mg every 8 weeks (mean [SD] age, 72.6 [8.2] years; 69% male). Mean baseline BCVA letter score (approximate Snellen) was 56.3 (20/80), 60.1 (20/63), and 57.6 (20/80), respectively, with 41, 37, and 51 participants completing week 48 and receiving a mean (SD) of 6.1 (0.4), 5.1 (0.5), and 7.0 (0.2) injections, including 68 of 78 (87%) treated with aflibercept, 8 mg, who maintained dosing intervals of 12 weeks or longer. In the treatment arms receiving aflibercept, 8 mg, every 12 and 16 weeks and aflibercept, 2 mg, every 8 weeks, LS mean BCVA change from baseline at week 48 was +9.5, +8.4, and +9.1 letters, respectively (estimated difference, 0.40; 95% CI, -4.4 to 5.2 letters for 8 mg every 12 weeks vs 2 mg every 8 weeks; -0.7; 95% CI, -4.6 to 3.2 letters for 8 mg every 16 weeks vs 2 mg every 8 weeks), and polypoidal lesions were absent in 37%, 47%, and 38% of participants, respectively, who completed week 48.31:Tc1c,In the Study of the Effects of High-Dose Aflibercept Injected Into the Eye of Patients With an Age-Related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye (PULSAR) phase 3 randomized clinical trial, treatment with aflibercept, 8 mg, demonstrated noninferior (4-letter margin) best-corrected visual acuity (BCVA) gains vs aflibercept, 2 mg, in participants with neovascular age-related macular degeneration (nAMD). This post hoc subgroup analysis evaluated clinical outcomes in participants with polypoidal choroidal vasculopathy (PCV). To compare the efficacy and safety of aflibercept, 8 mg vs 2 mg, monotherapy among participants with PCV in the PULSAR trial. This was a post hoc subgroup analysis of the PULSAR randomized clinical trial. The setting included hospitals and clinics in 12 countries where indocyanine green angiography (ICGA) was performed to identify PCV. Included were a subgroup of adults with nAMD enrolled in the PULSAR trial with ICGA-confirmed PCV. Study data were analyzed from August 2020 to July 2022. Participants were randomly assigned 1:1:1 to aflibercept, 8 mg, every 12 weeks or 16 weeks, or aflibercept, 2 mg, every 8 weeks, each after 3 initial monthly doses. From week 16, dosing intervals in the treatment arms receiving 8 mg every 12 weeks and every 16 weeks were shortened if predefined disease activity criteria were met at prespecified visits. Least-squares (LS) mean change in BCVA from baseline at week 48. A total of 139 participants were included in this analysis. ICGA-confirmed PCV was present in 44 participants in the treatment group receiving aflibercept, 8 mg, every 12 weeks (mean [SD] age, 72.2 [8.1] years; 50% male), 41 participants receiving 8 mg every 16 weeks (mean [SD] age, 73.2 [8.7] years; 63% male), and 54 participants receiving 2 mg every 8 weeks (mean [SD] age, 72.6 [8.2] years; 69% male). Mean baseline BCVA letter score (approximate Snellen) was 56.3 (20/80), 60.1 (20/63), and 57.6 (20/80), respectively, with 41, 37, and 51 participants completing week 48 and receiving a mean (SD) of 6.1 (0.4), 5.1 (0.5), and 7.0 (0.2) injections, including 68 of 78 (87%) treated with aflibercept, 8 mg, who maintained dosing intervals of 12 weeks or longer. In the treatment arms receiving aflibercept, 8 mg, every 12 and 16 weeks and aflibercept, 2 mg, every 8 weeks, LS mean BCVA change from baseline at week 48 was +9.5, +8.4, and +9.1 letters, respectively (estimated difference, 0.40; 95% CI, -4.4 to 5.2 letters for 8 mg every 12 weeks vs 2 mg every 8 weeks; -0.7; 95% CI, -4.6 to 3.2 letters for 8 mg every 16 weeks vs 2 mg every 8 weeks), and polypoidal lesions were absent in 37%, 47%, and 38% of participants, respectively, who completed week 48. Results of this post hoc analysis of the PULSAR randomized clinical trial in participants with PCV demonstrated similar visual and anatomic outcomes with aflibercept, 8 mg vs 2 mg, as administered in this trial, supporting the use of aflibercept, 8 mg, as an alternative monotherapy for PCV. ClinicalTrials.gov Identifier: NCT04423718.32:T11e7, Importance In the Study of the Effects of High-Dose Aflibercept Injected Into the Eye of Patients With an Age-Related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye (PULSAR) phase 3 randomized clinical trial, treatment with aflibercept, 8 mg, demonstrated noninferior (4-letter margin) best-corrected visual acuity (BCVA) gains vs aflibercept, 2 mg, in participants with neovascular age-related macular degeneration (nAMD). This post hoc subgroup analysis evaluated clinical outcomes in participants with polypoidal choroidal vasculopathy (PCV). Objective To compare the efficacy and safety of aflibercept, 8 mg vs 2 mg, monotherapy among participants with PCV in the PULSAR trial. Design, Setting, and Participants This was a post hoc subgroup analysis of the PULSAR randomized clinical trial. The setting included hospitals and clinics in 12 countries where indocyanine green angiography (ICGA) was performed to identify PCV. Included were a subgroup of adults with nAMD enrolled in the PULSAR trial with ICGA-confirmed PCV. Study data were analyzed from August 2020 to July 2022. Interventions Participants were randomly assigned 1:1:1 to aflibercept, 8 mg, every 12 weeks or 16 weeks, or aflibercept, 2 mg, every 8 weeks, each after 3 initial monthly doses. From week 16, dosing intervals in the treatment arms receiving 8 mg every 12 weeks and every 16 weeks were shortened if predefined disease activity criteria were met at prespecified visits. Main Outcomes and Measures Least-squares (LS) mean change in BCVA from baseline at week 48. Results A total of 139 participants were included in this analysis. ICGA-confirmed PCV was present in 44 participants in the treatment group receiving aflibercept, 8 mg, every 12 weeks (mean [SD] age, 72.2 [8.1] years; 50% male), 41 participants receiving 8 mg every 16 weeks (mean [SD] age, 73.2 [8.7] years; 63% male), and 54 participants receiving 2 mg every 8 weeks (mean [SD] age, 72.6 [8.2] years; 69% male). Mean baseline BCVA letter score (approximate Snellen) was 56.3 (20/80), 60.1 (20/63), and 57.6 (20/80), respectively, with 41, 37, and 51 participants completing week 48 and receiving a mean (SD) of 6.1 (0.4), 5.1 (0.5), and 7.0 (0.2) injections, including 68 of 78 (87%) treated with aflibercept, 8 mg, who maintained dosing intervals of 12 weeks or longer. In the treatment arms receiving aflibercept, 8 mg, every 12 and 16 weeks and aflibercept, 2 mg, every 8 weeks, LS mean BCVA change from baseline at week 48 was +9.5, +8.4, and +9.1 letters, respectively (estimated difference, 0.40; 95% CI, −4.4 to 5.2 letters for 8 mg every 12 weeks vs 2 mg every 8 weeks; −0.7; 95% CI, −4.6 to 3.2 letters for 8 mg every 16 weeks vs 2 mg every 8 weeks), and polypoidal lesions were absent in 37%, 47%, and 38% of participants, respectively, who completed week 48. Conclusions and Relevance Results of this post hoc analysis of the PULSAR randomized clinical trial in participants with PCV demonstrated similar visual and anatomic outcomes with aflibercept, 8 mg vs 2 mg, as administered in this trial, supporting the use of aflibercept, 8 mg, as an alternative monotherapy for PCV. Trial Registration ClinicalTrials.gov Identifier: NCT04423718 33:T635,To provide guidance on the recommended management of cancer in pregnant patients. A multidisciplinary Expert Panel convened and conducted a systematic review of the literature. The systematic review identified 450 eligible studies. Much of the evidence consisted of observational data, case series, and case reports. Management of cancer during pregnancy should be grounded in a values-based informed-consent process outlining maternal and fetal risks and anticipated benefits. Diagnostic evaluation should follow the as low as reasonably achievable (ALARA) principle, with timing of diagnostic studies individualized based on urgency of cancer detection, potential dangers of delay, and the balance of risks to both the pregnant patient and her embryo or fetus. Due to significant risk of harm to the developing embryo and/or fetus, systemic therapy should be deferred until the second trimester. Methotrexate, hormonal therapies, human epidermal growth factor receptor 2-targeted agents, vascular endothelial growth factor and poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and all cellular therapies are contraindicated during pregnancy, regardless of gestational age. For patients who wish to continue their pregnancy, delivery should be planned at or after 37 weeks, with the final chemotherapy dose scheduled 2-4 weeks before birth. Referral to psychosocial support services is essential to address emotional and practical challenges, reduce distress, and support shared decision making.Additional information is available at www.asco.org/survivorship-guidelines.34:T11ae, ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the

ASCO Guidelines Methodology Manual

. ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more. PURPOSE To provide guidance on the recommended management of cancer in pregnant patients. METHODS A multidisciplinary Expert Panel convened and conducted a systematic review of the literature. RESULTS The systematic review identified 450 eligible studies. Much of the evidence consisted of observational data, case series, and case reports. RECOMMENDATIONS Management of cancer during pregnancy should be grounded in a values-based informed-consent process outlining maternal and fetal risks and anticipated benefits. Diagnostic evaluation should follow the as low as reasonably achievable (ALARA) principle, with timing of diagnostic studies individualized based on urgency of cancer detection, potential dangers of delay, and the balance of risks to both the pregnant patient and her embryo or fetus. Due to significant risk of harm to the developing embryo and/or fetus, systemic therapy should be deferred until the second trimester. Methotrexate, hormonal therapies, human epidermal growth factor receptor 2–targeted agents, vascular endothelial growth factor and poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and all cellular therapies are contraindicated during pregnancy, regardless of gestational age. For patients who wish to continue their pregnancy, delivery should be planned at or after 37 weeks, with the final chemotherapy dose scheduled 2-4 weeks before birth. Referral to psychosocial support services is essential to address emotional and practical challenges, reduce distress, and support shared decision making. Additional information is available at www.asco.org/survivorship-guidelines . 35:T600,In the past few decades, advances in understanding of cancer biology have led to the development of highly effective conventional chemotherapies, targeted therapies that act on specific pathways that are critical to cancer growth, immune-based therapies, and cellular therapies such as haematopoietic cell transplantation and chimeric antigen receptor T cell therapy. However, the nephrotoxic effects of these therapies continue to pose substantial challenges, with many unanswered questions regarding the prevention, diagnosis and management of this nephrotoxicity. Further, a lack of consensus and precise guidance on kidney function estimation and drug dosing for patients with acute kidney disease or chronic kidney disease and for patients receiving kidney replacement therapy limits access to life-saving therapies and jeopardizes outcomes. In this Consensus Statement, we present guidance on the prevention, diagnosis and management of anticancer therapy nephrotoxicity for adult patients that was developed at the 34th Acute Disease Quality Initiative meeting, which convened an international panel of experts in nephrology, haematology, oncology, nephropathology, critical care, paediatric care and pharmacology. We also define a research agenda focused on preventing and mitigating anticancer therapy toxicity, maximizing early detection of nephrotoxicity and enabling optimal drug dosing in patients with kidney disease, with the goal of advancing cancer care and fulfilling the potential of these ground-breaking treatments.36:T2296,The ADQI consensus meeting was sponsored by Alexion, Baxter, Bioporto, BTG/SERB Pharmaceuticals, Calliditas, Medibeacon, Merck, Nova Biomedical, Novartis, Pfizer and SeaStar Medical. Sponsoring entities had no input in the discussions or in the final consensus statements or manuscript preparation. K.B. receives research support to her institution from StemLine Therapeutics. L.C. serves on the advisory boards of SERB and on speaker panels for SERB and Pfizer. She also serves as Editor-in-Chief of the Journal of Onco-Nephrology . R.F. had teaching honoraria from Vifor. M.F. serves on the advisory boards of GlaxoSmithKline and on speaker panels for Fresenius Medical Care, Jafron, B. Braun, Nipro and GlaxoSmithKline. He also serves on the editorial board for Kidney and Blood Pressure Research . L.G.F. reports research support from Baxter, Medibeacon, OrthoDiagnostics, SphingoTec and the NIHR. He has been on speaker panels for Fresenius Medical Care, Cytosorbents, SphingoTec and Vantive. I.G.G. reports an advisory board fee from T-knife Therapeutics, Inc. and support from NIH MSK Core Grant P30CA008748. S.L.G. receives consulting income from SeaStar Medical, BioPorto Diagnostics, Calcimedica, Mozarc Medical, Otsuka, Baxter Healthcare, Renibus Therapeutics and Novartis. He serves as a paid member of the Data Safety Monitoring Board for Silver Creek Therapeutics and Novartis. He serves on Speaker’s Panels for Baxter Healthcare and Fresenius Medical Care. He has stock options from MediBeacon, Inc. and serves as their Director of Clinical Development. He and his employer receive licensing royalties from RAIDAR Health. S.G. reports research support from the NIH, NIDDK K23DK125672 and R03DK141708. She also reports research funding from BTG International, Janssen, GE Healthcare and AstraZeneca, outside the submitted work. She is a consultant for Alexion, Mersana, MediBeacon and Orion Pharma. She founded and is Co-President Emeritus of the American Society of Onconephrology (unpaid). She also received speaker fees from Springer Inc. S.M.H. reports research support from Mayo Clinic Center for Clinical and Translational Science grant number UL1TR002377 and the Fulk Career Development Award. She serves as Review Section Editor for onconephrology for Nephrology Dialysis Transplantation . E.A.J. is supported by NIH grants R01DK129299 and P30CA008748. K.D.J. reports consultancy agreements with Novartis, Otsuka, Calliditas, George Clinicals, Vera Therapeutics and Travere Therapeutics; reports honoraria from the American Society of Nephrology and the International Society of Nephrology; is a paid contributor to UpToDate and is Section Editor for onconephrology for Nephrology Dialysis Transplantation ; serves on the editorial boards of American Journal of Kidney Diseases , CJASN , Clinical Kidney Journal , Frontiers in Nephrology , Journal of Onco-Nephrology and Kidney International ; and serves as the Editor-in-Chief of ASN Kidney News . S.K. reports consultancy agreement with George Clinicals, serves on the editorial boards of Advances in Kidney Disease and Health and Néphrologie et Thérapeutique , as a Review Editor for Frontiers in Nephrology and as a board member for the American Society of Onconephrology. A.K. administers funding from Amgen and Janssen for the University Health Network Onco-Nephrology Fellowship and serves as the President of the American Society of Onconephrology. H.J.L. receives research funding from Alexion (AstraZeneca), Nexcella, Janssen, Abbvie, Prothena and Protego. She has served in consultant/advisory roles to Alexion (AstraZeneca), Nexcella, Karyopharm, Arcellx, Abbvie and Pfizer. D.E.L. is supported by NIH grants R01DK125786, R01DK126685 and U01AG089040, has received research support from BioPorto, BTG International, Metro International Biotech LLC, Renibus Therapeutics, Inc. and Alexion Pharmaceuticals, has served as a consultant for Sidereal Therapeutics, MexBrain, Entrada Therapeutics, CardioRenal Systems, Inc. and Alexion Pharmaceuticals, and served as a Co-Chair of a Safety Monitoring Committee for EMD Serono Research and Development Institute, Inc. P.L. is an Associate Editor for Cardiorenal Medicine , Blood Purification and Frontiers in Nephrology and serves on the editorial board for the AKI section of the Journal of Nephrology . He has participated in speaker panels or advisory boards sponsored by AstraZeneca, Bayer, Jafron and GSK. J.M. is an editorial board member of Nephrology Dialysis Transplantation (Transplantation section). G.M. serves on the editorial boards of Kidney International , Kidney International Reports and the Journal of Onco-Nephrology . N.M. reports research support from NIH, R01DK137980; is a consultant for Otsuka, Asahi Kasei, Akebia and Sanofi; received honorarium from Elsevier; serves on the editorial board of Transplantation . M.O. received research funding from bioMérieux and Baxter, which was paid to the institution. A.P. has served on the advisory boards of GlaxoSmithKline, Otsuka, Astellas, and Teva Pharma and participated in speaker panels for Amgen, Menarini, AstraZeneca, Bayer, Alexion and Boehringer Lilly. Additionally, he serves on the editorial board for the Journal of Onco-Nephrology . M.A.P. serves as co-Editor-in-Chief of the Journal of Onco-Nephrology , Deputy Editor of Kidney360 and AKI Series Editor of Clinical Nephrology . He serves on editorial boards for Kidney International , KI Reports , the Journal of Nephrology and the American Journal of Medicine . D.R. served on advisory boards of Novartis and Alexion, had teaching honorariums from GSK, BMS, Roche, Novartis and Alexion, and is an UpToDate contributor. C.R. reports serving as Editor-in-Chief of Blood Purification and Cardiorenal Medicine and serving as speaker and having consultancy agreements with AstraZeneca, Aferetica, Asahi, Bayer, B. Braun, Baxter, bioMérieux, CytoSorbents, GE, Medica and Jafron. E.S. acts as a consultant for D.E. Shaw Research and serves on the Advisory Board for Mallinckrodt Pharmaceuticals. B.S. is Theme Editor for onconephrology for the Clinical Kidney Journal and on the editorial board of the Journal of Onco-Nephrology and Glomerular Diseases . V.Tesař is on the editorial board of the Clinical Kidney Journal and is Editor-in-Chief of Frontiers in Nephrology . He also served on the advisory board or received honoraria from AstraZeneca, Boehringer Ingelheim, Novartis, Otsuka, Travere and Vera. V.Torres serves as Academic Editor for PLoS One and is coordinator of the GFR Research Group of the American Society of Onconephrology. R.W. serves as an Associate Editor for the Journal of Onco-Nephrology and the Clinical Kidney Journal . B.T.W. serves as a consultant for Otsuka. D.Z.-O. reports research support from the NIH NCI R01CA291827, R01CA243014, R44CA268314, R44CA232954, R01DK138101. She has intellectual property with Galera Therapeutics and Perspective Therapeutics outside the submitted work. A.D.R., D.E.G., S.L., A.R., A.W. and M.H.R. declare no competing interests.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"VEGF Inhibitor: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on VEGF Inhibitor (modality). Clinician-written summaries and actionable practice insights. 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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/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.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":"10.1136/gutjnl-2026-338325","pmid":"42209191","title":"CPEB4 deficiency promotes vasculogenic mimicry and resistance to anti-angiogenic therapy in hepatocellular carcinoma","journal_title":"Gut","journal_issn":"0017-5749","published_at":"2026-05-28T00:00:00.000Z","url":"https://doi.org/10.1136/gutjnl-2026-338325","source_score":4,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-05T13:26:48.625Z","updated_at":"2026-06-05T13:26:48.625Z","tags":[{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"modality","value":"Anti-Angiogenic Therapy","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"modality","value":"VEGF Inhibitor","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"study_design","value":"Preclinical Study (In Vitro / In Vivo)","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"warning","value":"No explicit sample size is reported in the abstract; the sample_size tag has been omitted.","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"warning","value":"Study design is primarily preclinical (murine models and xenografts); 'mixed' age group reflects the use of both human and murine models rather than a defined clinical population.","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-338325","tag_type":"warning","value":"Two impact flags (safety_signal and practice_changing) were applied: 'safety_signal' reflects the resistance mechanism identified, and 'practice_changing' reflects the potential biomarker implication — use with caution as findings are preclinical only.","value_numeric":null}],"summaries":{"practice_takeaway":"Clinicians should be aware that low CPEB4 expression in HCC may predict reduced benefit from anti-VEGF therapies by enabling VEGF-independent vasculogenic mimicry. CPEB4 status could serve as a future biomarker to guide patient selection or combination strategies in advanced HCC.","what_studied":"This study examined whether CPEB4 (a translational regulator) suppresses vasculogenic mimicry (VM) and adaptive resistance to anti-VEGF therapy in hepatocellular carcinoma (HCC), using human and murine liver cancer models with genetic CPEB4 loss, xenografts, transcriptomic and ribosome profiling, and functional vascular assays.","key_result":"CPEB4 loss enhanced VM capacity in vitro and in vivo, preserved vascular channels under VEGF blockade, and sustained tumour viability — driven mechanistically by an EMT-associated translational programme with increased ribosome occupancy of EMT transcripts enriched for cytoplasmic polyadenylation elements.","limitations":"- No specific sample size (n) is reported in the abstract for human cohorts or experiments.\n- Causal directionality between CPEB4 loss, EMT, and clinical anti-angiogenic resistance remains to be confirmed in prospective human data.\n- Translational findings rely heavily on preclinical (murine/xenograft) models, which may not fully recapitulate human HCC biology."}},{"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":"10.1001/jamaophthalmol.2025.5098","pmid":"41411005","title":"Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy","journal_title":"JAMA Ophthalmology","journal_issn":"2168-6165","published_at":"2025-12-18T00:00:00.000Z","url":"https://doi.org/10.1001/jamaophthalmol.2025.5098","source_score":21,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2025-12-19","doi":"10.1001/jamaophthalmol.2025.5098","days":"30","issn":"2168-6165","rank":"10","field":"Clinical Medicine","score":"21","category":"Ophthalmology","categories":["Ophthalmology"],"_categories":["Ophthalmology"]},"pubmed":{"doi":"10.1001/jamaophthalmol.2025.5098","title":"Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: Post Hoc Analysis of the PULSAR Randomized Clinical Trial.","journal":"JAMA ophthalmology","methods":"","results":"$30","abstract":"$31","keywords":[],"pubmed_id":"41411005","conclusions":"","publication_date":"2025-12-18T00:00:00"},"crossref":{"DOI":"10.1001/jamaophthalmol.2025.5098","URL":"https://doi.org/10.1001/jamaophthalmol.2025.5098","ISSN":["2168-6165"],"link":[{"URL":"https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2842906/jamaophthalmology_lee_2025_oi_250078_1765408778.1565.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy"],"author":[{"given":"Won Ki","family":"Lee","sequence":"first","affiliation":[{"name":"Nune Eye Hospital, Seoul, Republic of Korea"}]},{"given":"Tien Y.","family":"Wong","sequence":"additional","affiliation":[{"name":"Tsinghua Medicine, School 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Reported risks include AKI in nearly 1 in 10 patients on systemic therapy; cisplatin nephrotoxicity 25–30%, ifosfamide 3–30%, methotrexate 2–30%, gemcitabine‑TMA 2–4%; VEGF‑inhibitor hypertension 30–80% and proteinuria 20–63% (nephrotic syndrome 2–6%); and ICI‑AKI 2–5%.","limitations":"This is expert consensus, not an interventional study; many recommendations lack randomized validation and some depend on resource availability (for example, access to measured GFR and drug monitoring). Incidence estimates vary across studies owing to heterogeneous AKD definitions and populations.","practice_takeaway":"Adopt KHA/KHR workflows: use CKD‑EPI creatinine–cystatin C (or measured GFR when estimates are unreliable), check kidney labs before dosing and within ~1 week after exposure, and tailor surveillance by agent. For VEGF inhibitors, monitor blood pressure early and often and check urine protein each cycle; for ICIs, avoid PPIs, pause therapy for suspected AKD and start glucocorticoids early; for cytotoxics, use established measures (e.g., urine alkalinization and drug‑level–guided leucovorin/glucarpidase for high‑dose methotrexate; check and replace magnesium with cisplatin)."}}],"initialOffset":8,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"VEGF Inhibitor"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"VEGF Inhibitor"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"VEGF Inhibitor"}}}]]

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