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:T6c3,Based on the results from SOLTI-PATRICIA trial (NCT02448420) cohorts A/B, a direct comparison with standard-of-care treatments is needed to evaluate the efficacy and safety of palbociclib, trastuzumab and endocrine therapy (ET) in PAM50-luminal A/B pretreated patients. SOLTI-PATRICIA cohort C is a randomised, multicentre, prospective, open-label, phase II study. Pretreated patients with HER2-positive, HR-positive, and PAM50-Luminal A/B ABC were randomised 1:1 to receive either i) the triplet regimen or ii) trastuzumab-based treatment of physician's choice (TPC). Patients allocated in the TPC arm were eligible for re-randomization upon disease progression, if the inclusion criteria were still met. The primary endpoint was investigator-assessed progression-free survival (PFS) per RECIST 1.1. 264 participants were pre-screened between August 2019-2023, and 73 patients were randomised (including seven re-randomisations). In the TPC arm: 48.5% were treated with trastuzumab plus chemotherapy, 39.4% with T-DM1 and 12.1 % with trastuzumab plus ET. The triplet was associated with a significantly better PFS compared to TPC (stratified hazard ratio=0.52 [95% CI 0.29-0.95]; two-sided p=0.03). PFS rates after 24 months were 24.0% with the triplet and 4.3% in the TPC arm. The overall response rate was 18.9% (95% CI 8.6-35.7) and 7.1% (95% CI 1.2-25.0), respectively. In the triplet arm, grade ≥3 adverse events occurred in 61.5% of patients, with neutropenia being the most frequent (53.9%). No permanent discontinuations due to toxicity were observed. Combining palbociclib, trastuzumab, and ET was safe and improved significantly PFS, compared to TPC in previously treated HER2-positive, PAM50 luminal A/B ABC patients.31:T9dc,Abstract Purpose: Based on the results from SOLTI-PATRICIA trial (NCT02448420) cohorts A/B, a direct comparison with standard-of-care treatments is needed to evaluate the efficacy and safety of palbociclib, trastuzumab, and endocrine therapy (ET) in PAM50 luminal A/B pretreated patients. Patients and Methods: SOLTI-PATRICIA cohort C is a randomized, multicenter, prospective, open-label, phase II study. Pretreated patients with HER2-positive, hormone receptor–positive, and PAM50 luminal A/B advanced breast cancer were randomized 1:1 to receive either i) the triplet regimen or ii) trastuzumab-based treatment of physician’s choice (TPC). Patients allocated in the TPC arm were eligible for re-randomization upon disease progression, if the inclusion criteria were still met. The primary endpoint was investigator-assessed progression-free survival (PFS) per RECIST version 1.1. Results: A total of 264 participants were prescreened from August 2019 to 2023, and 73 patients were randomly assigned (including seven re-randomizations). In the TPC arm, 48.5% were treated with trastuzumab plus chemotherapy, 39.4% with trastuzumab emtansine, and 12.1% with trastuzumab plus ET. The triplet was associated with a significantly better PFS compared with TPC [stratified hazard ratio = 0.52; 95% confidence interval (CI), 0.29–0.95; two-sided P = 0.03]. PFS rates after 24 months were 24.0% with the triplet and 4.3% in the TPC arm. The overall response rate was 18.9% (95% CI, 8.6–35.7) and 7.1% (95% CI, 1.2–25.0), respectively. In the triplet arm, grade ≥3 adverse events occurred in 61.5% of patients, with neutropenia being the most frequent (53.9%). No permanent discontinuations due to toxicity were observed. Conclusions: Combining palbociclib, trastuzumab, and ET was safe and significantly improved PFS, compared with TPC, in previously treated patients with HER2-positive, PAM50 luminal A/B advanced breast cancer. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"CDK4/6 Inhibitor: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on CDK4/6 Inhibitor (modality). Clinician-written summaries and actionable practice insights. 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mixed tags are inferred from the multi-condition, multi-drug nature of included cases.","value_numeric":null},{"paper_doi":"10.1093/ced/llag350","tag_type":"warning","value":"Level of evidence assigned as 3 (systematic review of case reports/series) rather than 1, because the underlying data are case-level reports without controlled comparators—causality cannot be confirmed for most associations.","value_numeric":null},{"paper_doi":"10.1093/ced/llag350","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the prognostic signal in melanoma (90.5% favourable outcomes), but this is based on a small subset with available data (n=42) and should be interpreted cautiously.","value_numeric":null}],"summaries":{"what_studied":"A PRISMA-compliant systematic review of published cases (January 1975–January 2026) reporting new-onset vitiligo following exposure to any pharmacological agent, characterising implicated drug classes, clinical patterns, latency, and proposed pathogenic mechanisms across 258 individual cases.","key_result":"Immune checkpoint inhibitors (ICIs) were the most implicated drug class (72/258, 27.9%), followed by topical immune modifiers/sensitisers (46/258, 17.8%), biologic immunomodulators (44/258, 17.1%), and targeted therapies (43/258, 16.7%). Vitiligo onset most often occurred 3–6 months after treatment start (66/256, 25.8%). Among malignancy-associated cases with outcome data, 77.9% (74/95) had favourable oncological outcomes, rising to 90.5% (38/42) in melanoma cases.","limitations":"- All cases are from published reports, introducing selection and publication bias; causality cannot be established for many associations.\n- Outcome data were available for only a subset of malignancy-associated cases (95 of a larger cohort), limiting generalisability.\n- Narrative synthesis only—no meta-analysis—due to clinical heterogeneity across drug classes and case designs.","practice_takeaway":"When a patient on an ICI, biologic, or targeted therapy develops new depigmentation, drug-associated vitiligo should be on the differential—onset typically within 3–6 months of starting treatment. In melanoma patients, vitiligo development may signal a favourable treatment response and should be communicated as a potentially positive prognostic marker rather than a reason to stop therapy."}},{"doi":"10.1093/jnci/djag256","pmid":"42530873","title":"A multicenter, phase I/II trial of anastrozole, palbociclib, trastuzumab, and pertuzumab in hormone receptor (HR)-positive, HER2-positive metastatic breast cancer (ASPIRE)","journal_title":"JNCI: Journal of the National Cancer Institute","journal_issn":"0027-8874","published_at":"2026-07-30T00:00:00.000Z","url":"https://doi.org/10.1093/jnci/djag256","source_score":14,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-11T13:26:21.632Z","updated_at":"2026-08-11T13:26:21.632Z","tags":[{"paper_doi":"10.1093/jnci/djag256","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"brand","value":"Arimidex","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"brand","value":"Herceptin","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"brand","value":"Ibrance","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"brand","value":"Perjeta","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"condition","value":"HR-Positive HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"condition","value":"Metastatic Breast Cancer","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"generic","value":"anastrozole","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"generic","value":"palbociclib","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"generic","value":"pertuzumab","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"generic","value":"trastuzumab","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"modality","value":"Aromatase Inhibitor","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"modality","value":"HER2-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"sample_size","value":"n=29","value_numeric":29},{"paper_doi":"10.1093/jnci/djag256","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"study_design","value":"Phase I/II Trial","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"warning","value":"Median OS was not reached, so OS benefit cannot be fully assessed from available follow-up data.","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"warning","value":"Phase I/II single-arm design (no randomized comparator); level of evidence assigned as 3 reflects non-randomized controlled trial status.","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"warning","value":"Sample size is very small (n=29 response-evaluable); efficacy estimates should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1093/jnci/djag256","tag_type":"warning","value":"Sex not explicitly reported in the abstract, but assumed female given the breast cancer population — clinicians should verify in the full paper.","value_numeric":null}],"summaries":{"what_studied":"The ASPIRE trial evaluated frontline anastrozole + palbociclib + trastuzumab + pertuzumab in previously untreated HR-positive, HER2-positive metastatic breast cancer (MBC) in a multicenter Phase I/II design; Phase I used 3+3 dose escalation and Phase II used an optimal Simon two-stage design.","key_result":"Palbociclib MTD was 125 mg (no dose-limiting toxicities at 100 mg or 125 mg). In 29 response-evaluable patients, 6-month clinical benefit rate was 97% (n=28; 95% CI: 82–99%), median PFS was 24.9 months (95% CI: 17.2–44.8), and median OS was not reached at 39.4 months follow-up. Grade 3–4 treatment-related adverse events occurred in 62% of patients (n=18), mostly hematologic.","limitations":"Single-arm trial without a randomized comparator limits causal inference. Very small sample size (n=29 response-evaluable) reduces precision of efficacy estimates. Hormone receptor and HER2 subgroup results cannot be generalized without confirmatory randomized data.","practice_takeaway":"This chemotherapy-free regimen of anastrozole + palbociclib + trastuzumab + pertuzumab showed high clinical benefit (97%) and durable PFS (~25 months) in HR+/HER2+ MBC, but remains investigational pending randomized trial confirmation. Monitor closely for hematologic toxicity, which drove most grade 3–4 adverse events."}},{"doi":"10.1016/j.esmoop.2026.108311","pmid":"42492369","title":"Somatic BRCA alterations in breast cancer are associated with distinct biological and clinical patterns according to germline BRCA status","journal_title":"ESMO Open","journal_issn":"2059-7029","published_at":"2026-07-23T00:00:00.000Z","url":"https://doi.org/10.1016/j.esmoop.2026.108311","source_score":34,"is_retracted":false,"is_open_access":null,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":false},"created_at":"2026-07-31T13:36:56.274Z","updated_at":"2026-07-31T13:36:56.274Z","tags":[{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"condition","value":"Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"condition","value":"ER-Positive HER2-Negative Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"condition","value":"Triple-Negative Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"generic","value":"BRCA1/2 germline and somatic testing","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"modality","value":"Comprehensive Genomic Profiling","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"sample_size","value":"n=2978","value_numeric":2978},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"warning","value":"'Practice_changing' flag applied cautiously — the finding challenges routine interpretation of somatic-only BRCA results, but prospective validation is pending.","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"warning","value":"Sex not explicitly stated as female-only in the abstract, but breast cancer cohort composition is assumed predominantly female; verify if male BC cases were included.","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"warning","value":"The paper is published in 2026 and references a Japanese national database (C-CAT); findings may not generalize to non-Japanese populations.","value_numeric":null},{"paper_doi":"10.1016/j.esmoop.2026.108311","tag_type":"warning","value":"TTD (time to treatment discontinuation) is used as a surrogate for efficacy; it conflates discontinuation due to progression, toxicity, or other reasons.","value_numeric":null}],"summaries":{"what_studied":"This study examined 2,978 breast cancer cases from the C-CAT database, categorizing patients into four groups based on combined germline (g) and somatic (s) BRCA status (g+/s+, g+/s−, g−/s+, g−/s−) to assess differences in genomic landscape, HRD features, and clinical outcomes (TTD) across ER+/HER2− and TNBC subtypes.","key_result":"g−/s+ tumors had distinct biology from g+/s+ tumors: they were enriched for PIK3CA/TP53 mutations and non-BRCA HRD alterations (52%), while g+/s+ tumors showed classical HRD signatures. In ER+/HER2− BC, germline BRCA positivity was linked to shorter CDK4/6 inhibitor TTD (g+/s+ HR 1.3, P<0.001), but g−/s+ tumors performed similarly to g−/s− tumors. In TNBC, immune checkpoint inhibitor outcomes were not associated with any BRCA group.","limitations":"Retrospective database design limits causal inference; time to treatment discontinuation is a surrogate endpoint, not overall survival; germline–somatic concordance may be affected by tumor heterogeneity and biopsy site (somatic alterations more common in metastatic specimens).","practice_takeaway":"Do not interpret somatic BRCA alterations in isolation — a g−/s+ result does not carry the same therapeutic or prognostic meaning as a germline BRCA mutation. Always integrate germline status and broader genomic context (e.g., HRD landscape, PIK3CA/TP53 co-mutations) when counseling patients and selecting therapy."}},{"doi":"10.1038/s41523-026-01002-2","pmid":"42386766","title":"Identifying the window of aggressive postpartum breast cancer based on the 21-gene Oncotype DX® test in women with HR+, HER2-negative breast cancer","journal_title":"npj Breast Cancer","journal_issn":"2374-4677","published_at":"2026-07-01T00:00:00.000Z","url":"https://doi.org/10.1038/s41523-026-01002-2","source_score":38,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-13T17:42:36.918Z","updated_at":"2026-07-13T17:42:36.918Z","tags":[{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"brand","value":"Oncotype DX","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"condition","value":"Hormone Receptor-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"condition","value":"Postpartum Breast Cancer","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"modality","value":"Gene Expression Profiling","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"modality","value":"Ovarian Function Suppression","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"sample_size","value":"n=385","value_numeric":385},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"warning","value":"HER2-negative status is specified in the inclusion criteria but HER2 testing methodology is not described in the abstract or supplementary content provided.","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"warning","value":"The DOI prefix '10.1038/s41523-026-01002-2' uses a non-standard year format (026); this may be a formatting artifact but could not be verified from the provided text.","value_numeric":null},{"paper_doi":"10.1038/s41523-026-01002-2","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — findings are from a single institution with a modest PPBC subgroup and relatively short follow-up; external validation is needed before broad clinical adoption.","value_numeric":null}],"summaries":{"what_studied":"This single-institution retrospective cohort study evaluated how postpartum timing affects the 21-gene Oncotype DX Recurrence Score (RS) in 385 young women with HR+, HER2-negative breast cancer, comparing nulliparous patients, those within 10 years postpartum, and those >10 years postpartum.","key_result":"Diagnosis within 1 year of childbirth was linked to a 13.2-point higher RS vs. nulliparous patients (p < 0.001). Defining PPBC as ≤3 years postpartum was associated with increased odds of RS category shift (OR 2.83, p = 0.001). Despite more aggressive treatment in the PPBC group, 3-year PPBC IDFS was 89.0% vs. 93.7% in all others (p = 0.39).","limitations":"Single-institution retrospective design limits generalizability; follow-up period may be insufficient to detect IDFS differences given the small PPBC subgroup; confounding by treatment selection (more chemotherapy, OFS, CDK4/6 inhibitors in PPBC) cannot be fully excluded.","practice_takeaway":"Women diagnosed within 3 years of childbirth with HR+/HER2− breast cancer are likely to have significantly elevated Oncotype DX scores and should be assessed carefully for escalated adjuvant therapy. Clinicians should consider the postpartum window — especially the first 1–3 years — when interpreting RS results and planning treatment."}},{"doi":"10.1016/j.ajo.2026.06.020","pmid":"42341974","title":"Corneal Epithelial Alterations Associated With CDK4/6 Inhibitor Therapy in Hormone Receptor–Positive Breast Cancer","journal_title":"American Journal of Ophthalmology","journal_issn":"0002-9394","published_at":"2026-06-24T00:00:00.000Z","url":"https://doi.org/10.1016/j.ajo.2026.06.020","source_score":3,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-29T13:22:43.646Z","updated_at":"2026-06-29T13:22:43.646Z","tags":[{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"condition","value":"Corneal Epithelial Disease","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"condition","value":"Hormone Receptor-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"condition","value":"Punctate Epitheliopathy","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"condition","value":"Vortex Keratopathy","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"generic","value":"abemaciclib","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"generic","value":"palbociclib","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"generic","value":"ribociclib","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"modality","value":"Aromatase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"sample_size","value":"n=132","value_numeric":132},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"study_design","value":"Retrospective Comparative Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"warning","value":"All participants were postmenopausal women; findings may not generalize to premenopausal patients or other sexes.","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"warning","value":"Brand names for ribociclib, palbociclib, and abemaciclib are not mentioned in the paper and were omitted from tags accordingly.","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"warning","value":"Cross-sectional design precludes causal inference; the direct cytostatic mechanism proposed by authors remains speculative.","value_numeric":null},{"paper_doi":"10.1016/j.ajo.2026.06.020","tag_type":"warning","value":"The incomplete OSDI response rate in the CDKAI group is acknowledged by authors as a limitation for symptom burden conclusions.","value_numeric":null}],"summaries":{"what_studied":"This retrospective comparative cross-sectional study evaluated corneal epithelial changes in 132 postmenopausal women: 45 receiving a CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) plus an aromatase inhibitor (CDKAI group), 44 on aromatase inhibitor monotherapy, and 43 age-matched controls with no systemic oncologic therapy.","key_result":"Punctate epitheliopathy (PE) was present in 44.4% of CDKAI group eyes vs. 4.7% in the aromatase inhibitor-only group and 2.3% in controls (P < .001); all moderate (13.3%) and severe/complicated (8.9%) PE cases were exclusive to the CDKAI group. Vortex keratopathy appeared in 13.3% of CDKAI patients vs. 0% in both comparator groups (P = .025). Tear film parameters and symptom scores (OSDI) did not differ across groups.","limitations":"- Retrospective cross-sectional design prevents establishing causality or temporal progression of corneal changes.\n- Incomplete OSDI response rate in the CDKAI group limits conclusions about true symptom burden.\n- PE severity was not associated with treatment duration, leaving the dose–response relationship unclear.","practice_takeaway":"Patients on CDK4/6 inhibitor therapy for HR+ breast cancer should have proactive corneal surface evaluation with fluorescein staining, even if they report few ocular symptoms. Vortex keratopathy and punctate epitheliopathy can occur in the absence of measurable tear film dysfunction, suggesting a direct cytostatic mechanism rather than dry-eye–related injury."}},{"doi":"10.1007/s43032-026-02134-3","pmid":"42277398","title":"p16 Beyond Senescence: Cancer Biology Lessons Applied to Endometriosis","journal_title":"Reproductive Sciences","journal_issn":"1933-7191","published_at":"2026-06-11T00:00:00.000Z","url":"https://doi.org/10.1007/s43032-026-02134-3","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-20T13:24:47.244Z","updated_at":"2026-06-20T13:24:47.244Z","tags":[{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"condition","value":"Endometriosis","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"generic","value":"azithromycin","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"generic","value":"everolimus","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"generic","value":"quercetin","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"generic","value":"rapamycin","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"modality","value":"mTOR Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"modality","value":"Senolytic","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"warning","value":"Azithromycin is discussed as a senotherapeutic agent, which is an off-label and experimental use not yet in standard clinical practice.","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"warning","value":"No sample size tag assigned — this is a narrative review with no primary patient cohort.","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"warning","value":"Study design is a single-author narrative review; systematic search methods and inclusion/exclusion criteria are not described, increasing risk of bias.","value_numeric":null},{"paper_doi":"10.1007/s43032-026-02134-3","tag_type":"warning","value":"Therapeutic recommendations (mTOR inhibition, senolytics) are speculative and based on indirect or preclinical evidence; no RCT data in endometriosis are presented.","value_numeric":null}],"summaries":{"what_studied":"This narrative review examined the context-dependent roles of p16INK4a in endometriosis, focusing on its links to cellular senescence, the senescence-associated secretory phenotype (SASP), the immune microenvironment, and potential therapeutic modulation via senotherapeutics and mTOR inhibition.","key_result":"Endometriosis lesions contain two distinct cell populations: those with **high p16** (linked to cellular senescence, chronic inflammation, immunosuppressive microenvironment, and aberrant tissue remodeling) and those with **low p16** (linked to sustained CDK4/6 activity, proliferative capacity, and enhanced plasticity with reduced SASP dependence). mTOR inhibition emerged as a candidate indirect strategy to attenuate p16/p21 expression and SASP.","limitations":"- Narrative review design with no systematic search protocol, introducing selection bias.\n- No original patient data or quantitative synthesis; all conclusions are synthesized from heterogeneous prior studies.\n- Mechanistic framework is largely conceptual, with limited direct clinical evidence for proposed senotherapeutic strategies in endometriosis.","practice_takeaway":"Clinicians should recognize that p16 expression in endometriosis is not uniformly tumor-suppressive—its high expression marks a pro-inflammatory, immunosuppressive state, while its loss enables cell proliferation. Therapeutic focus should shift toward preventing irreversible senescence and restoring endometrial function, with mTOR inhibition (e.g., rapamycin) as a potential avenue, though clinical evidence remains preliminary."}},{"doi":"10.1158/1078-0432.ccr-25-0650","pmid":"41587113","title":"Role of ctDNA in Predicting the Outcome of Patients with Hormone Receptor–Positive, HER2-Negative Advanced Breast Cancer Treated with First-line Ribociclib and Letrozole: BioItaLEE Trial","journal_title":"Clinical Cancer Research","journal_issn":"1078-0432","published_at":"2026-04-28T00:00:00.000Z","url":"https://doi.org/10.1158/1078-0432.ccr-25-0650","source_score":45,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-10T13:20:47.361Z","updated_at":"2026-05-10T13:20:47.361Z","tags":[{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"brand","value":"Kisqali","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"condition","value":"Advanced Breast Cancer","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"condition","value":"HER2-Negative Breast Cancer","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"condition","value":"Hormone Receptor-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"generic","value":"letrozole","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"generic","value":"ribociclib","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"modality","value":"Aromatase Inhibitor","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"modality","value":"Circulating Tumor DNA (ctDNA) Biomarker","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"sample_size","value":"n=287","value_numeric":287},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"study_design","value":"Prospective Biomarker Study (Phase 3b)","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"warning","value":"Hazard ratios are reported for ctDNA subgroups but the directionality for the 'no new mutations' HR=0.45 should be interpreted as favoring the mutation-free group — phrasing in the abstract is slightly ambiguous.","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"warning","value":"The postmenopausal-only population limits generalizability to premenopausal patients with HR+/HER2− advanced breast cancer.","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-0650","tag_type":"warning","value":"The study is labeled 'phase 3b' but functions as a prospective biomarker sub-study rather than a randomized controlled trial — level of evidence reflects prospective cohort design.","value_numeric":null}],"summaries":{"what_studied":"This phase 3b prospective study (BioItaLEE) evaluated the prognostic and predictive value of baseline and early dynamic ctDNA in 287 postmenopausal patients with HR+/HER2− advanced breast cancer receiving first-line ribociclib plus letrozole, with ctDNA assessed at baseline, Day 15 of Cycle 1 (C1D15), Cycle 2 Day 1 (C2D1), and first imaging.","key_result":"Median PFS was 23.4 months. No detectable mutation at baseline (57% of patients) was linked to better PFS (HR=0.41). Among mutation-positive patients, early ctDNA clearance by C1D15 or C2D1 was seen in ~47–52% and also associated with improved PFS (HR=0.51 and 0.44, respectively). In initially ctDNA-negative patients, emergence of new mutations was associated with higher progression risk (HR=0.45 favoring those without new mutations).","limitations":"- ctDNA analysis was not available for all enrolled patients at every time point (up to 81 patients missing at some time points), which may introduce selection bias.\n- No matched tissue genomics or functional validation of identified alterations was described, limiting mechanistic interpretation.\n- Results require prospective validation before clinical implementation, as acknowledged by the authors.","practice_takeaway":"Consider baseline ctDNA testing in HR+/HER2− advanced breast cancer patients starting ribociclib/letrozole — absence of detectable mutations or early clearance by Cycle 2 Day 1 signals better outcomes. Early ctDNA dynamics (especially TP53, MYC, CDK4/6 pathway alterations) may help identify patients at risk for early progression who may need closer monitoring or treatment adjustment."}},{"doi":"10.1016/j.breast.2026.104786","pmid":"41999684","title":"Integrating PIK3CA Testing into Clinical Practice for Advanced HR+/HER2- Breast Cancer: An Expert Consensus","journal_title":"The Breast","journal_issn":"0960-9776","published_at":"2026-04-10T00:00:00.000Z","url":"https://doi.org/10.1016/j.breast.2026.104786","source_score":23,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:49:45.686Z","updated_at":"2026-05-07T22:49:45.686Z","tags":[{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"brand","value":"Faslodex","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"brand","value":"Ibrance","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"brand","value":"Itovebi","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"brand","value":"Kisqali","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"condition","value":"Hormone Receptor-Positive HER2-Negative Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"condition","value":"Metastatic Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"generic","value":"alpelisib","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"generic","value":"capivasertib","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"generic","value":"fulvestrant","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"generic","value":"inavolisib","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"generic","value":"palbociclib","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"modality","value":"Liquid Biopsy","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"modality","value":"Next-Generation Sequencing","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"modality","value":"PI3K Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"study_design","value":"Expert Consensus / Delphi Study","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"warning","value":"Brand name 'Itovebi' is the FDA-approved trade name for inavolisib; European trade name may differ. Verify local formulary.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"warning","value":"Sample size tag is not applicable here as this is a consensus document with no patient cohort enrolled.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"warning","value":"Some referenced regulatory approvals (e.g., European Commission July 2025 for inavolisib) are stated as forthcoming relative to the paper's April 2026 publication date — these have not been independently verified.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104786","tag_type":"warning","value":"This is an Italian expert panel consensus, not a systematic review or RCT; recommendations reflect expert opinion and may not fully apply outside Italian/European practice contexts.","value_numeric":null}],"summaries":{"what_studied":"A multidisciplinary Italian expert panel used a modified Delphi method (2 rounds, June–October 2025) to build consensus on PIK3CA molecular testing in advanced HR+/HER2- breast cancer, covering sample selection, analytical methods, sensitivity thresholds, reporting standards, and clinical integration.","key_result":"23 of 29 statements reached 100% agreement. Key recommendations include: NGS preferred over PCR (full exon 1–20 coverage); liquid biopsy valid but tissue is reference matrix; LOD ≤0.5% VAF required for plasma assays; any activating PIK3CA mutation (canonical or non-canonical) in either tissue or plasma is sufficient for PI3K inhibitor eligibility; inavolisib + palbociclib + fulvestrant is the preferred first-line regimen for PIK3CA-mutated patients progressing during or within 12 months of adjuvant endocrine therapy (INAVO120: PFS HR 0.42, OS HR 0.67, ORR 62.7% vs 28%).","limitations":"Consensus was confined to Italian experts, limiting geographic generalizability. The Delphi format reflects expert opinion rather than primary data; no new clinical trial data were generated. Concordance thresholds and LOD recommendations rely on existing (often industry-sponsored) trial data.","practice_takeaway":"Test all advanced HR+/HER2- breast cancer patients for PIK3CA using NGS panels covering the full coding sequence; a positive result in tissue or plasma at any VAF is actionable. For patients progressing on or within 12 months of adjuvant endocrine therapy with a confirmed PIK3CA mutation, offer inavolisib + palbociclib + fulvestrant as first-line metastatic treatment."}},{"doi":"10.1016/j.breast.2026.104769","pmid":"42048902","title":"Real-world effectiveness of CDK4/6 inhibitors in older patients with HR+/HER2- advanced breast cancer: a sub-analysis of the multicenter, PALMARES-2 study","journal_title":"The Breast","journal_issn":"0960-9776","published_at":"2026-03-31T00:00:00.000Z","url":"https://doi.org/10.1016/j.breast.2026.104769","source_score":5,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-08T13:23:45.162Z","updated_at":"2026-05-08T13:23:45.162Z","tags":[{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"brand","value":"Ibrance","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"brand","value":"Kisqali","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"brand","value":"Verzenio","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"condition","value":"HR+/HER2- Advanced Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"generic","value":"abemaciclib","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"generic","value":"palbociclib","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"generic","value":"ribociclib","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"modality","value":"Endocrine Therapy","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"sample_size","value":"n=1982","value_numeric":1982},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"study_design","value":"Real-World Evidence / Retrospective-Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"warning","value":"Longer median follow-up in the palbociclib cohort (vs. ribociclib/abemaciclib) is a material confound acknowledged by the authors; CDK4/6i cross-drug comparisons should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"warning","value":"References in the full text are listed as placeholders ([1], [2], etc.) without citation details, limiting verification of supporting evidence.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"warning","value":"Sex is inferred as female given the breast cancer population; the paper does not explicitly report the proportion of male patients.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104769","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — this is a real-world observational sub-analysis; no randomized head-to-head comparison of CDK4/6i in older patients exists.","value_numeric":null}],"summaries":{"what_studied":"Real-world effectiveness of first-line endocrine therapy (ET) plus CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) was compared between older (>75 years, n=302) and younger (≤75 years, n=1680) patients with HR+/HER2- advanced breast cancer in the multicenter Italian PALMARES-2 cohort (n=1982; data cut-off Jan 31, 2024).","key_result":"Older patients had significantly better real-world PFS than younger patients (median 34.9 vs. 33.8 months; aHR 0.77, 95% CI 0.67–0.90, p=0.001). In older patients, palbociclib was as effective as abemaciclib and more effective than ribociclib—the opposite of what was seen in younger patients (p for interaction <0.001). Among palbociclib-treated patients, older patients had better rwPFS than younger (median 38.9 vs. 26.6 months; aHR 0.69, 95% CI 0.57–0.84, p<0.001). Despite better rwPFS, older patients had worse OS (median 61.1 vs. 66.6 months; aHR 1.18, p<0.001), likely driven by fewer subsequent treatment lines and competing causes of death.","limitations":"- Observational design with potential residual confounding; no formal geriatric assessment tools (e.g., G8, ADL, IADL) used to quantify frailty beyond age and comorbidities.\n- Longer follow-up in the palbociclib cohort vs. ribociclib/abemaciclib cohorts may bias CDK4/6i comparisons in favor of palbociclib.\n- Imbalance in sample size and baseline features across CDK4/6i sub-cohorts limits cross-drug comparisons.","practice_takeaway":"For HR+/HER2- advanced breast cancer patients older than 75, ET plus CDK4/6i is highly effective—don't withhold it based on age alone. Palbociclib appears equally effective as abemaciclib in this age group and offers better tolerability and fewer drug–drug interactions, making it the preferred CDK4/6i choice for most patients over 75."}},{"doi":"10.1200/jco-25-02643","pmid":"41802242","title":"VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor–Positive/HER2−/PIK3CA Wild-Type Advanced Breast Cancer","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-03-09T00:00:00.000Z","url":"https://doi.org/10.1200/jco-25-02643","source_score":76,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-20T13:23:32.044Z","updated_at":"2026-05-20T13:23:32.044Z","tags":[{"paper_doi":"10.1200/jco-25-02643","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"brand","value":"Faslodex","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"brand","value":"Ibrance","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"condition","value":"Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"condition","value":"PIK3CA Wild-Type Breast Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"generic","value":"fulvestrant","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"generic","value":"gedatolisib","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"generic","value":"palbociclib","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"modality","value":"PI3K/mTOR Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"modality","value":"Selective Estrogen Receptor Degrader","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"sample_size","value":"n=392","value_numeric":392},{"paper_doi":"10.1200/jco-25-02643","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"warning","value":"Fulvestrant monotherapy was used as the control arm to meet regulatory requirements; it is no longer standard of care in all countries, so the magnitude of PFS benefit vs. fulvestrant may not directly translate to comparative benefit over currently preferred second-line regimens (e.g., oral SERDs, inavolisib combinations).","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"warning","value":"OS data are immature at primary analysis (median follow-up 10.1 months); crossover from the fulvestrant arm to gedatolisib-based therapy was permitted, which may attenuate future OS differences.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"warning","value":"Study sponsor (Celcuity Inc.) was involved in trial design, data analysis, and manuscript development; multiple authors have financial relationships with Celcuity.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02643","tag_type":"warning","value":"The trial enrolled only PIK3CA wild-type patients (Study 1); PIK3CA-mutated cohort (Study 2) results are pending and may change the overall positioning of gedatolisib.","value_numeric":null}],"summaries":{"what_studied":"Phase III randomized trial (VIKTORIA-1) comparing gedatolisib triplet (gedatolisib + palbociclib + fulvestrant) and gedatolisib doublet (gedatolisib + fulvestrant) vs. fulvestrant monotherapy in 392 adults with HR+/HER2−/PIK3CA wild-type advanced breast cancer who progressed on or after a CDK4/6 inhibitor and nonsteroidal aromatase inhibitor; median follow-up 10.1 months.","key_result":"Median PFS was 9.3 months (triplet) and 7.4 months (doublet) vs. 2.0 months (fulvestrant); HR 0.24 (95% CI 0.17–0.35) and HR 0.33 (95% CI 0.24–0.48), both P < .001. Objective response rates were 31.5% (triplet), 28.3% (doublet), and 1.0% (fulvestrant). Grade ≥3 neutropenia was 62.3% in the triplet vs. 0.8% in the doublet; grade ≥3 stomatitis was 19.2% and 12.3%, respectively. Treatment discontinuation due to TRAEs was low (2.3% triplet, 3.1% doublet). Interim OS data were immature and did not cross significance boundaries.","limitations":"- ESR1 mutation status was not assessable in most patients (plasma samples not prospectively collected), limiting biomarker-guided interpretation.\n- Only palbociclib was tested as the CDK4/6i partner; applicability to ribociclib or abemaciclib combinations is unknown.\n- OS data are immature; crossover from fulvestrant to gedatolisib arms complicates future OS analysis.","practice_takeaway":"For patients with HR+/HER2−/PIK3CA wild-type advanced breast cancer progressing after CDK4/6i + aromatase inhibitor, adding gedatolisib to fulvestrant (with or without palbociclib) cut the risk of progression or death by 67–76% vs. fulvestrant alone. The doublet avoids high-grade neutropenia and may be preferred when avoiding re-exposure to a CDK4/6i; the triplet showed numerically longer PFS in several subgroups including prior palbociclib-treated patients."}},{"doi":"10.1158/1078-0432.ccr-25-2882","pmid":"41335375","title":"Palbociclib, Trastuzumab, and Endocrine Therapy in Pretreated HER2-Positive and PAM50 Luminal Advanced Breast Cancer: Randomized Phase II, SOLTI-1303 PATRICIA Trial","journal_title":"Clinical Cancer Research","journal_issn":"1078-0432","published_at":"2025-12-03T00:00:00.000Z","url":"https://doi.org/10.1158/1078-0432.ccr-25-2882","source_score":77,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-08","doi":"10.1158/1078-0432.ccr-25-2882","days":"14","issn":"1078-0432","rank":"10","field":"Clinical Medicine","score":"77","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1158/1078-0432.CCR-25-2882","title":"Palbociclib, trastuzumab and endocrine therapy in pretreated HER2-positive and PAM50 luminal advanced breast cancer: randomised phase II, SOLTI-1303 PATRICIA trial.","journal":"Clinical cancer research : an official journal of the American Association for Cancer Research","methods":"","results":"264 participants were pre-screened between August 2019-2023, and 73 patients were randomised (including seven re-randomisations). In the TPC arm: 48.5% were treated with trastuzumab plus chemotherapy, 39.4% with T-DM1 and 12.1 % with trastuzumab plus ET. The triplet was associated with a significantly better PFS compared to TPC (stratified hazard ratio=0.52 [95% CI 0.29-0.95]; two-sided p=0.03). PFS rates after 24 months were 24.0% with the triplet and 4.3% in the TPC arm. The overall response rate was 18.9% (95% CI 8.6-35.7) and 7.1% (95% CI 1.2-25.0), respectively. In the triplet arm, grade ≥3 adverse events occurred in 61.5% of patients, with neutropenia being the most frequent (53.9%). No permanent discontinuations due to toxicity were observed.","abstract":"$30","keywords":[],"pubmed_id":"41335375","conclusions":"","publication_date":"2025-12-03T00:00:00"},"crossref":{"DOI":"10.1158/1078-0432.ccr-25-2882","URL":"https://doi.org/10.1158/1078-0432.ccr-25-2882","ISSN":["1078-0432","1557-3265"],"link":[{"URL":"https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-25-2882/3708870/ccr-25-2882.pdf","content-type":"application/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-25-2882/3723636/ccr-25-2882.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-25-2882/3723636/ccr-25-2882.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"OF1-OF10","type":"journal-article","issue":null,"score":1,"title":["Palbociclib, Trastuzumab, and Endocrine Therapy in Pretreated HER2-Positive and PAM50 Luminal Advanced Breast Cancer: Randomized Phase II, SOLTI-1303 PATRICIA Trial"],"author":[{"given":"Eva","family":"Ciruelos","sequence":"first","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"2Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain."},{"name":"3HM Hospitales, Madrid, Spain."}]},{"given":"Tomás","family":"Pascual","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"4Medical Oncology, Institute of Cancer and Blood Diseases, Hospital Clinic of Barcelona, Barcelona, Spain."},{"name":"5Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain."},{"name":"6Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain."}]},{"given":"Guillermo","family":"Villacampa","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"7Statistics Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain."}]},{"given":"Sonia","family":"Pernas","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"8Medical Oncology Department, Institut Catala d’ Oncologia (ICO)- Institute of Biomedical Research of Bellvitge (IDIBELL), L’Hospitalet del Llobregat, Barcelona, Spain."}]},{"given":"Rodrigo","family":"Sanchez-Bayona","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"2Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain."}]},{"given":"José","family":"Ponce","sequence":"additional","affiliation":[{"name":"9Medical Oncology, Hospital General Universitario Dr. Balmis, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain."},{"name":"10GEICAM Spanish Breast Cancer Group, Madrid, Spain."}]},{"given":"Blanca","family":"Cantos","sequence":"additional","affiliation":[{"name":"11Hospital Universitario Puerta de Hierro, Madrid, Spain."}]},{"given":"Santiago","family":"Escrivá-de-Romaní","sequence":"additional","affiliation":[{"name":"12Medical Oncology Department, Vall d’Hebron University Hospital, and Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain."}]},{"given":"Antonia","family":"Perelló","sequence":"additional","affiliation":[{"name":"13Medical Oncology Department, Hospital Universitario Son Espases, Palma De Mallorca, Spain."}]},{"given":"Esther","family":"Sanfeliu","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"5Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain."},{"name":"14Pathology Department, Hospital Clínic de Barcelona, Barcelona, Spain."}]},{"given":"Patricia","family":"Galvan","sequence":"additional","affiliation":[{"name":"5Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain."}]},{"given":"Alvaro","family":"Montaño","sequence":"additional","affiliation":[{"name":"15Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Sevilla, Spain."}]},{"given":"Eduardo","family":"Martínez","sequence":"additional","affiliation":[{"name":"16Consorcio Hospitalario Provincial de Castellón, Castellón de la Plana, Spain."}]},{"given":"Ana","family":"Lopez","sequence":"additional","affiliation":[{"name":"10GEICAM Spanish Breast Cancer Group, Madrid, Spain."},{"name":"17Complejo Asistencial Universitario de León, León, Spain."}]},{"given":"Mireia","family":"Mele","sequence":"additional","affiliation":[{"name":"18Medical Oncology, Hospital Universitari Sant Joan de Reus, Reus, Spain."}]},{"given":"Juan","family":"de la Haba","sequence":"additional","affiliation":[{"name":"10GEICAM Spanish Breast Cancer Group, Madrid, Spain."},{"name":"19Medical Oncology Department, Hospital Universitario Reina Sofia, Cordoba, Spain."}]},{"given":"Javier","family":"Cortés","sequence":"additional","affiliation":[{"name":"6Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain."},{"name":"20International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain."},{"name":"21IOB Madrid, Hospital Beata Maria Ana, Madrid, Spain."}]},{"given":"Antonio","family":"Mulero-Sánchez","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."}]},{"given":"Juan M.","family":"Ferrero-Cafiero","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."}]},{"given":"Mafalda","family":"Oliveira","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"12Medical Oncology Department, Vall d’Hebron University Hospital, and Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain."}]},{"given":"Lorea","family":"Villanueva","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."}]},{"given":"Xavier","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"22Medical Oncology, IOR - Instituto Oncologico Dr. Rosell, Hospital General de Catalunya, Barcelona, Spain."}]},{"given":"Patricia","family":"Villagrasa","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"23Reveal Genomics, S.L Barcelona, Barcelona, Spain."}]},{"given":"Aleix","family":"Prat","sequence":"additional","affiliation":[{"name":"1SOLTI Cancer Research Group, Barcelona, Spain."},{"name":"4Medical Oncology, Institute of Cancer and Blood Diseases, Hospital Clinic of Barcelona, Barcelona, Spain."},{"name":"5Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain."},{"name":"23Reveal Genomics, S.L Barcelona, Barcelona, Spain."}]}],"funder":[{"id":[{"id":"10.13039/100004319","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100004319","name":"Pfizer","doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2026,1,6]]},"member":"1086","prefix":"10.1158","source":"Crossref","volume":null,"created":{"date-time":"2025-12-03T16:04:32Z","timestamp":1764777872000,"date-parts":[[2025,12,3]]},"indexed":{"date-time":"2026-01-06T16:31:26Z","timestamp":1767717086180,"date-parts":[[2026,1,6]]},"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-25-2882/771469/Palbociclib-Trastuzumab-and-Endocrine-Therapy-in"}},"subtitle":[],"deposited":{"date-time":"2026-01-06T16:28:49Z","timestamp":1767716929000,"date-parts":[[2026,1,6]]},"issn-type":[{"type":"print","value":"1078-0432"},{"type":"electronic","value":"1557-3265"}],"published":{"date-parts":[[2026,1,6]]},"publisher":"American Association for Cancer Research (AACR)","reference":null,"short-title":[],"update-policy":"https://doi.org/10.1158/crossmark_policy","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"original-title":[],"container-title":["Clinical Cancer Research"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,1,6]]},"references-count":0,"short-container-title":[],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1158/1078-0432.ccr-25-2882","is_oa":false,"title":"Palbociclib, Trastuzumab, and Endocrine Therapy in Pretreated HER2-Positive and PAM50 Luminal Advanced Breast Cancer: Randomized Phase II, SOLTI-1303 PATRICIA Trial","updated":"2026-01-10T04:46:20+00:00","published_date":"2025-12-03","best_oa_location":null}},"created_at":"2026-01-11T11:19:33.869Z","updated_at":"2026-01-17T09:03:27.421Z","tags":[{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"generic","value":"palbociclib","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"generic","value":"trastuzumab","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"modality","value":"CDK4/6 Inhibitor","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"modality","value":"Endocrine Therapy","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"modality","value":"HER2-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"sample_size","value":"n=73","value_numeric":73},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"warning","value":"Comparator arm consisted of heterogeneous regimens (trastuzumab + chemotherapy, T-DM1, or trastuzumab + endocrine therapy).","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"warning","value":"Only investigator-assessed PFS is reported; no OS data provided.","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-2882","tag_type":"warning","value":"Open-label phase II randomized design with small N and re-randomization in the physician’s choice arm may affect interpretation.","value_numeric":null}],"summaries":{"what_studied":"A multicenter, open-label, randomized phase II trial compared palbociclib + trastuzumab + endocrine therapy with trastuzumab-based treatment of physician’s choice in pretreated HER2-positive, HR-positive, PAM50-luminal A/B advanced breast cancer; the primary endpoint was investigator-assessed PFS per RECIST 1.1. From August 2019–2023, 264 were pre-screened and 73 were randomized (including 7 re-randomizations).","key_result":"The triplet improved PFS versus physician’s choice (HR 0.52, 95% CI 0.29–0.95; p=0.03); 24-month PFS rates were 24.0% with the triplet and 4.3% with physician’s choice. ORR was 18.9% (95% CI 8.6–35.7) for the triplet versus 7.1% (95% CI 1.2–25.0), and in the triplet arm grade ≥3 AEs occurred in 61.5% with neutropenia in 53.9% and no permanent discontinuations due to toxicity.","limitations":"Open-label phase II study with a small randomized sample (n=73) and allowance for re-randomization in the physician’s choice arm. The comparator was heterogeneous (trastuzumab + chemotherapy, T-DM1, or trastuzumab + endocrine therapy), and outcomes were investigator-assessed.","practice_takeaway":"In selected pretreated HR+/HER2+ PAM50-luminal A/B advanced breast cancer, adding palbociclib to trastuzumab and endocrine therapy prolonged PFS versus trastuzumab-based options. Expect frequent neutropenia; monitor counts, noting no permanent discontinuations were reported."}}],"initialOffset":11,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"CDK4/6 Inhibitor"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"CDK4/6 Inhibitor"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"CDK4/6 Inhibitor"}}}]]

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