Annals of Oncology最新文献

{"title":"DART (NCI/SWOG S1609): Comprehensive Final Results from Dual Checkpoint Inhibition with CTLA-4 and PD-1 Blockade in Rare Cancers.","authors":"S P Patel, M Othus, Y K Chae, T Azenkot, C Alviz, S Threlkel, C Haymaker, H Z Streicher, C M Magner, H X Chen, E Sharon, C W Ryan, C D Blanke, R Kurzrock","doi":"10.1016/j.annonc.2026.04.004","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.004","url":null,"abstract":"<p><strong>Background: </strong>We summarize final results of the NCI/SWOG S1609 trial, whose objective was to evaluate efficacy signals across 53 refractory rare cancer cohorts treated with dual CTLA-4 and PD-1 inhibition.</p><p><strong>Patients and methods: </strong>A prospective, open-label, multicenter phase 2 trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks) was conducted (N=53 cohorts). A statistical framework was established to evaluate each cohort in a two-stage design. The primary end point was objective response rate (ORR), with progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR, ORR plus stable disease >6 months), i-outcomes, and toxicity as secondary and exploratory endpoints.</p><p><strong>Results: </strong>Overall, 798 previously treated patients were enrolled onto S1609/DART; 727 eligible patients received treatment; 1083 national (USA) sites opened the trial. Twenty-four of 53 cohorts (45%) demonstrated clinical activity, defined as ≥2 patients with confirmed response. Median (range) ORR was 12% (0-75%); CBR, 27% (0-75%). Median (range) 2-year PFS was 10% (0-75%); 3-year OS was 23% (0-100%). PFS at 6 months was moderately correlated with 1- and 3-year OS. Patients who attained an iOR versus OR had similar OS. Altogether, 82 patients (11% of the 727 enrolled patients) had an iPFS of ≥2 years. Immune-related toxicity rates were comparable to prior studies. Adverse events (AEs) led to treatment discontinuation in 102 patients (14%). The most common AEs were fever, diarrhea, and rash/pruritis. Patients alive at 6 months who discontinued treatment due to immune-related toxicity had longer OS than those who discontinued treatment for other reasons.</p><p><strong>Conclusion: </strong>Patients with multiple refractory rare cancer types derived meaningful response to ipilimumab plus nivolumab treatment. More robust characterization of biologically defined subsets is underway to optimize therapeutic selection.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Simple Plan: Chemotherapy-Sparing Approaches to Early Stage and Regional Seminoma and Non-Seminoma.","authors":"L Nappi, A Thor, T Tandstad, A Heidenreich, D Escobar, B Hu, A D'Souza, L Einhorn, N Adra, C Cary, T Masterson, C Kollmannsberger, R J Hamilton, G Ozgun, P Black, C Conduit, A L Harzstark, G Daugaard, P Albers, S Eggener, S Kern, K Fizazi, B Tran, A Bagrodia, N Nicolai, G Palmieri, F E Millard, B J Roth, S Daneshmand, C Nichols","doi":"10.1016/j.annonc.2026.04.005","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.005","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.","authors":"C Cremolini, M Chalabi, E Elez, M Fassan, M Gelli, D Goéré, D P Modest, C Montagut, P Osterlund, J Ricke, J Seligmann, J Taieb, T Yoshino, L Wyrwicz, M Ducreux","doi":"10.1016/j.annonc.2026.03.005","DOIUrl":"10.1016/j.annonc.2026.03.005","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Determinants of Response to Alpelisib Plus Fulvestrant in the SOLAR-1 Trial.","authors":"D Juric, H S Rugo, A Reising, K Vervier, C Ma, E M Ciruelos, S Loibl, C F Singer, J Sohn, M Campone, P Conte, H Iwata, F Ghaznawi, M Miller, T Taran, F Su, F André","doi":"10.1016/j.annonc.2026.04.003","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.003","url":null,"abstract":"<p><strong>Background: </strong>Approximately 40% of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer (ABC) have PIK3CA alterations, which contributes to endocrine therapy resistance. Alpelisib, an α-selective phosphatidylinositol 3-kinase inhibitor and degrader, given in combination with fulvestrant, is approved for the treatment of PIK3CA-mutated, HR+, HER2- ABC, based on the SOLAR-1 trial. Aside from PIK3CA, other gene alterations are associated with poor prognosis and limited response to treatment in this patient population.</p><p><strong>Patients and methods: </strong>In this retrospective analysis, we performed tissue-based next-generation sequencing of 398 patients (237 PIK3CA-altered, 161 PIK3CA-wild type) from SOLAR-1. Progression-free survival (PFS) correlative analysis was performed in the PIK3CA-altered cohort.</p><p><strong>Results: </strong>PIK3CA-altered and PIK3CA-wild type tumors had distinct genomic profiles. In the PIK3CA-altered cohort, patients who received alpelisib plus fulvestrant had a median PFS (mPFS) of 11.01 months versus 5.55 months for those receiving placebo plus fulvestrant (P=0.0004). Patients in the lowest tumor mutational burden quartile as well as those with FGFR1 or FGFR2 alterations derived greater PFS benefit from alpelisib plus fulvestrant versus placebo plus fulvestrant (18.5 versus 3.22 months; HR 0.38; 95% CI 0.21-0.68. FGFR1 12.71 versus 3.75 months; HR 0.38; 95% CI 0.17-0.81; P=0.32. FGFR2: 9.63 versus 2.78 months; HR 0.31; 95% CI 0.1-0.94; P=0.29); patients with MYC or RAD21 alterations derived limited PFS benefit. Cox and multi-task machine learning models identified lower Eastern Cooperative Oncology Group performance status, prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) treatment, and PTEN or TP53 alterations among the most deleterious factors for PFS in the PIK3CA-altered cohort.</p><p><strong>Conclusions: </strong>Alpelisib plus fulvestrant provides clinical benefit for patients with PIK3CA-altered, HR+, HER2- ABC across a range of concomitant alterations, including those previously implicated in endocrine therapy or CDK4/6i resistance. Machine learning models identified factors including gene mutations that influenced PFS.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Curious Incident of the T-DXd Arm Killed at (DESTINY-Breast) Eleven O'Clock: Statistical Concerns.","authors":"Armando Orlandi","doi":"10.1016/j.annonc.2026.04.001","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.001","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to 'Long-term outcomes with adjuvant CDK4/6 inhibitors: who benefits most?': [Annals of Oncology. Volume 37, Issue 2, February 2026, Pages 133-135].","authors":"T A O'Meara, H J Burstein","doi":"10.1016/j.annonc.2026.02.001","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.02.001","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer\": [Ann Oncol 36 (2025) 76-88].","authors":"D E Rathkopf, M R Patel, A D Choudhury, D Rasco, N Lakhani, J E Hawley, S Srinivas, A Aparicio, V Narayan, K D Runcie, H Emamekhoo, Z R Reichert, M H Nguyen, A L Wells, R Kandimalla, C Liu, S Suryawanshi, J Han, J Wu, V K Arora, M Pourdehnad, A J Armstrong","doi":"10.1016/j.annonc.2026.01.016","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.01.016","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial\": [Ann Oncol 36 (2025) 775-785].","authors":"E Felip, C I Rojas, M Schenker, D M Kowalski, I A Casarini, T Csöszi, M A N Şendur, J Martins, A Calles Blanco, C-C Wang, M Wang, R A L Ramirez Fallas, H Yoshioka, S Nair, X Song, X Deng, M Lala, R Eiras, T Takahashi","doi":"10.1016/j.annonc.2026.02.002","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.02.002","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial.","authors":"R Dent, Z Shao, P Schmid, J Cortes, D W Cescon, S Saji, K H Jung, T Bachelot, S Wang, E M Ramírez, G Basaran, A Stradella, R Mathiba, S-C Chen, K Shen, Á Wéber, N Battelli, N Niikura, T Luo, Y S Chae, N Fischbach, G Garbaos, A Patera, K Zhao, P Vuković, M J Maxwell, T Traina","doi":"10.1016/j.annonc.2026.03.008","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.03.008","url":null,"abstract":"<p><strong>Background: </strong>Prognosis is poor and treatment options are limited for patients with previously untreated, advanced triple-negative breast cancer (TNBC), especially for those who are not candidates for immunotherapy.</p><p><strong>Patients and methods: </strong>In the randomised, open-label, phase III TROPION-Breast02 trial, patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option were randomised 1:1 to datopotamab deruxtecan (Dato-DXd; 6 mg/kg intravenously every 3 weeks) or investigator's choice of chemotherapy. Randomisation was stratified by geographic location, disease-free interval and programmed cell death ligand-1 status. Dual primary endpoints were progression-free survival (PFS; blinded independent central review per Response Evaluation Criteria in Solid Tumors, version 1.1) and overall survival (OS). Efficacy analyses were performed in the intention-to-treat population. Safety analyses included all patients who received ≥1 dose of study treatment.</p><p><strong>Results: </strong>Between 16 May 2022 and 11 June 2024, 644 patients were randomised to Dato-DXd (n = 323) or chemotherapy (n = 321). Median PFS was 10.8 months (95% confidence interval [CI] 8.6-13.0) with Dato-DXd and 5.6 months (95% CI 5.0-7.0) with chemotherapy (hazard ratio 0.57 [99% CI 0.44-0.73]; P < 0.0001). Median OS was 23·7 months (95% CI 19.8-25.6) and 18.7 months (95% CI 16.0-21.8) with Dato-DXd and chemotherapy, respectively (hazard ratio 0.79 [95.01% CI 0.64-0.98]; P = 0.029). Treatment-related adverse events (TRAEs) of grade ≥3 were reported in 105 (33%) and 89 (29%) patients who received Dato-DXd and chemotherapy, respectively, and TRAEs led to treatment discontinuation in 14 (4%) and 23 (7%) patients. There were no treatment-related deaths in either arm.</p><p><strong>Conclusions: </strong>Dato-DXd demonstrated significantly improved PFS and OS versus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. Safety was consistent with the known profile for Dato-DXd.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine Release Symptoms rather than Syndromes: A call for Granular Reporting of Cytokine Related Adverse Events in Clinical Trials.","authors":"J-D Fumet, M Roulleaux Dugage, F-X Danlos, T Hueso, D J Pinato, J Luke, I Melero Bermejo, P Lorusso, J Brody, K Harrington, N H Segal, A Diab, E Gerralda Cabanas, T Marron, R Houot, S Champiat, A Marabelle","doi":"10.1016/j.annonc.2026.03.006","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.03.006","url":null,"abstract":"<p><strong>Background: </strong>T-cell redirecting therapies, notably CAR T-cells and bispecific antibodies, have revolutionized the treatment of hematologic malignancies. Their rapid expansion into solid tumors, alongside the emergence of next-generation agents, such as immunocytokines and CD28-costimulatory bispecifics, has brought Cytokine Release Syndrome (CRS) to the forefront of clinical oncology. However, the absence of a unified grading system for these novel constructs remains a critical barrier to drug development and patient safety. Current toxicity management relies on disparate grading scales leading to inconsistent reporting and hindering cross-trial comparisons. A fundamental challenge lies in the diagnostic ambiguity created by the significant clinical and temporal overlap between CRS, infusion-related reactions (IRRs), and other diagnosis. While fever, hypotension, and hypoxia are common denominators, their distinct pathophysiological drivers necessitate divergent therapeutic interventions.</p><p><strong>Proposal: </strong>We advocate for a paradigm shift from aggregate syndromic grading toward a granular, longitudinal reporting framework. This approach prioritizes the precise documentation of symptom kinetics, specific interventions (e.g., exact vasopressor requirements, oxygen flow rates), and real-time biomarker integration By capturing high-fidelity data, researchers can retrospectively apply evolving criteria and develop more tailored, evidence-based management algorithms.</p><p><strong>Conclusion: </strong>Transitioning to a standardized, symptom-driven reporting model is essential to navigate the complexities of \"Immuno-oncology 2.0.\" Such a framework will harmonize safety assessments across global trials and ultimately optimize the therapeutic index of next-generation immunotherapies.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}