Annals of Oncology最新文献

{"title":"Targeting regulatory T cells for cancer immunotherapy: promises and pitfalls","authors":"O. Mirallas,&nbsp;G. Pretelli,&nbsp;M. Balsa,&nbsp;P. Jiménez-Labaig,&nbsp;A. Hernando-Calvo,&nbsp;H. Nathan Tan,&nbsp;P.N. Selvadurai,&nbsp;P. Tallón de Lara,&nbsp;M. Vieito,&nbsp;J. Martin-Liberal,&nbsp;K.J. Harrington,&nbsp;S. Champiat,&nbsp;E. Garralda","doi":"10.1016/j.annonc.2026.04.015","DOIUrl":"10.1016/j.annonc.2026.04.015","url":null,"abstract":"<div><h3>Background</h3><div>Regulatory T cells (Tregs) form a distinct subset of CD4⁺ T cells essential for maintaining immune balance and preventing autoimmunity by expressing CD25 and CTLA-4. Tregs, which are defined by the expression of the transcription factor FOXP3 in mice, restrain excessive immune activation through mechanisms such as interleukin 10 (IL-10) expression, transforming growth factor-β expression, metabolic regulation, acting as an IL-2 cytokine sink, and cell-to-cell interaction through co-inhibitory receptors. Although they are indispensable for immune tolerance, Tregs can be co-opted by tumors, where their suppressive activity promotes immune escape. High Treg infiltration within the tumor microenvironment has been linked to variable prognosis depending on the tumor type, highlighting Tregs’ contradictory roles as both guardians of tolerance and enablers of tumor progression.</div></div><div><h3>Design</h3><div>In this review, we summarized Treg biology, Tregs’ contribution to cancer immunity, and emerging therapeutic strategies designed to modulate or deplete Tregs. We conducted a targeted literature review using PubMed/MEDLINE, Web of Science, <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, and American Society of Clinical Oncology/European Society of Medical Oncology meeting libraries, complemented by manual reference screening. We also discussed the limitations of existing therapeutic approaches and outlined future directions.</div></div><div><h3>Results</h3><div>Efforts to therapeutically modulate Tregs have focused on three main strategies: depletion (e.g. anti-CD25, anti-CCR4, or anti-CCR8 antibodies), functional blockade (e.g. targeting CTLA-4 or TIGIT), and disruption of metabolic pathways (e.g. adenosine or PI3K signaling) that support Tregs’ biological functions. Although preclinical studies have shown that targeting Tregs has antitumor effects, clinical trials have demonstrated variable efficacy and toxicity , reflecting the fine balance between immune activation and tolerance. Newer approaches aim to selectively impair intratumoral Tregs while preserving peripheral immune control, guided by T-cell subsets such as FOXP3⁺Helios⁺CCR8⁺ cells, which may help predict therapeutic response.</div></div><div><h3>Conclusion</h3><div>A deeper understanding of Treg regulation is needed to unlock their therapeutic potential without compromising immune equilibrium.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1049-1065"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Including tumor-infiltrating lymphocytes into the PREDICT prognostic model for triple-negative breast cancer survival","authors":"Y. Wang,&nbsp;D. Drubay,&nbsp;S.F. Jonas,&nbsp;J. Dixon-Douglas,&nbsp;B. Acs,&nbsp;S. Adams,&nbsp;F. André,&nbsp;S. Badve,&nbsp;G. Bataillon,&nbsp;J.M. Carter,&nbsp;S. Chia,&nbsp;V. Cockenpot,&nbsp;M.A. Colleoni,&nbsp;C. Criscitiello,&nbsp;G. Curigliano,&nbsp;G.M.H.E. Dackus,&nbsp;S. Demaria,&nbsp;C. Denkert,&nbsp;C.H.M. van Deurzen,&nbsp;M.V. Dieci,&nbsp;S. Michiels","doi":"10.1016/j.annonc.2026.04.011","DOIUrl":"10.1016/j.annonc.2026.04.011","url":null,"abstract":"<div><h3>Background</h3><div>Stromal tumor-infiltrating lymphocytes (sTILs) are a strong prognostic marker in patients with triple-negative breast cancer (TNBC). We aimed to incorporate sTILs into the PREDICT model for women with early-stage TNBC to guide chemotherapy decisions.</div></div><div><h3>Patients and methods</h3><div>We included 3698 women with early-stage TNBC, diagnosed between 1979 and 2017, from two pooled cohorts with sTILs scored according to international guidelines to update PREDICT version 2.3. The updated model, PREDICT_sTILs, is a Cox regression model with sTILs and the PREDICT prognostic index as predictors and breast cancer-specific survival as the outcome. Internal–external validation was conducted using leave-one-region-out cross-validation, with calibration assessed by the observed-to-expected (O/E) ratio and discrimination by area under the curve (AUC). We compared the clinical values of PREDICT_sTILs and PREDICT through decision curve analysis, examining net true high-risk and low-risk classifications across risk thresholds of 10-year breast cancer mortality above 8%-15%.</div></div><div><h3>Results</h3><div>Among the 3698 patients, 1806 received chemotherapy while 1892 were chemotherapy-naïve. Chemotherapy-treated patients had a median age of 50 years, a tumor size of 25 mm, and one positive lymph node. The chemotherapy-naïve patients had a median age of 55 years, a tumor size of 20 mm, and 0 positive lymph nodes. Within 5 and 10 years, 741 and 860 deaths were attributed to breast cancer, respectively. PREDICT_sTILs showed strong internal–external validity, with comparable calibration and discrimination at both time points: pooled O/E ratios of 0.98 [95% confidence interval (CI) 0.69-1.41] at 5 years and 0.99 (95% CI 0.72-1.35) at 10 years, and AUCs of 0.74 (95% CI 0.72-0.77) and 0.74 (95% CI 0.70-0.78), respectively. Compared with PREDICT, PREDICT_sTILs identified 19-60 additional net true low-risk patients and 3-10 additional net true high-risk patients per 1000 chemotherapy-naïve patients at the risk thresholds of 8%-15% at 10 years.</div></div><div><h3>Conclusion</h3><div>Adding sTILs to PREDICT improves its ability to inform chemotherapy decisions for early-stage patients with TNBC, especially in identifying low-risk individuals who may safely forgo chemotherapy.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1093-1105"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760279","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":"Lung cancer brain metastases management at the dawn of personalized medicine: are we ready to break the barriers?","authors":"A. Mavrikios,&nbsp;M. Bortolot,&nbsp;C. Le Péchoux,&nbsp;J. Remon,&nbsp;A. Botticella,&nbsp;M. Aldea,&nbsp;P.D. Brown,&nbsp;C.G. Rusthoven,&nbsp;P. Lavaud,&nbsp;M. Frélaut,&nbsp;P. Abdayem,&nbsp;D. Lavigne,&nbsp;A. Camps-Maléa,&nbsp;B. Besse,&nbsp;D. Planchard,&nbsp;F. Barlesi,&nbsp;J. Jacob,&nbsp;P. Gougis,&nbsp;S. Knafo,&nbsp;C. Chargari,&nbsp;A. Levy","doi":"10.1016/j.annonc.2026.04.014","DOIUrl":"10.1016/j.annonc.2026.04.014","url":null,"abstract":"<div><div>Brain metastases occur in nearly half of patients with lung cancer and significantly impair survival and quality of life. Historically, limited blood–brain barrier penetration and low intracranial efficacy of systemic therapies restricted treatment options. However, advances in immune checkpoint inhibitors and next-generation central nervous system-penetrant targeted therapies have reshaped the therapeutic landscape, improving intracranial control and patient outcomes. In parallel, stereotactic radiotherapy has emerged as a precise and effective local treatment with a more favorable safety profile than whole-brain radiotherapy. The integration of systemic and local approaches, guided by personalized medicine, offers new opportunities to optimize central nervous system disease control. Nevertheless, these advances raise key challenges regarding treatment sequencing, patient selection, and risk-adapted strategies. This review summarizes the evolving management of lung cancer brain metastases and highlights future directions for clinical trial design, emphasizing the integration of clinical, biological, and radiological tools to guide individualized treatment strategies.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1030-1048"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy for patients with circulating tumour DNA-positive, stage II colon cancer (CIRCULATE)—an AIO/ABCSG trial","authors":"G. Folprecht,&nbsp;S. Stasik,&nbsp;A. Reinacher-Schick,&nbsp;L. Weiss,&nbsp;E. Goekkurt,&nbsp;L. Jacobasch,&nbsp;L. Conradi,&nbsp;A. Kröcher,&nbsp;R.-D. Hofheinz,&nbsp;R. Liersch,&nbsp;U.M. Martens,&nbsp;J. Chater,&nbsp;M. Fuchs,&nbsp;J.U. Riera Knorrenschild,&nbsp;J. Schubert,&nbsp;A. Klimova,&nbsp;L. Reinhardt,&nbsp;C. Sperling,&nbsp;J. von Tresckow,&nbsp;J. Weitz,&nbsp;C. Thiede","doi":"10.1016/j.annonc.2026.05.001","DOIUrl":"10.1016/j.annonc.2026.05.001","url":null,"abstract":"<div><h3>Background</h3><div>Adjuvant chemotherapy provides limited benefit in unselected stage II colon cancer. Post-operative circulating tumour DNA (ctDNA) has higher prognostic value than classical clinical markers, with ctDNA positivity indicating an unfavourable outcome.</div></div><div><h3>Patients and methods</h3><div>Patients with Union for International Cancer Control stage II, mismatch repair proficient/microsatellite stable colon cancer were tested for ctDNA using an academic, tumour-informed, next-generation sequencing-based test. ctDNA-positive patients were randomly assigned 2:1 to CHEMO (capecitabine ± oxaliplatin) or observation (OBS). ctDNA-negative patients were randomly assigned 1:4 to OBS or OFF-STUDY. ctDNA results were not disclosed in the OBS group. The primary endpoint was disease-free survival (DFS) in ctDNA-positive patients. All differences were tested using one-sided log-rank tests. The trial ended early due to funding expiry.</div></div><div><h3>Results</h3><div>From June 2020 to July 2025, 2126 patients were screened in Germany and Austria. Overall, 1396 patients (2.9% ctDNA-positive) were randomly assigned: 1083 to OFF-STUDY, 287 to OBS, and 26 to CHEMO, of whom 81% started therapy. DFS and overall survival (OS) were significantly worse in ctDNA-positive versus ctDNA-negative patients [3-year DFS 52% versus 87%, hazard ratio (HR) 4.28, 95% confidence interval (CI) 2.32-7.93, <em>P</em> &lt; 0.001; 3-year OS 88% versus 98%, HR 5.48, 95% CI 1.64-18.28, <em>P</em> = 0.001]. In the intention-to-treat (ITT) cohort, the between-arm differences were not significant (3-year recurrence 36% versus 62%, HR 0.48, 95% CI 0.17-1.33, <em>P</em> = 0.075; 3-year DFS 61% versus 38%, HR 0.55, 95% CI 0.21-1.48, <em>P</em> = 0.12). In the per-protocol analysis (excluding untreated CHEMO patients), time to recurrence and DFS were improved with CHEMO compared with OBS (3-year recurrence 19% versus 62%, HR 0.23, 95% CI 0.06-0.87, <em>P</em> = 0.009; 3-year DFS 77% versus 38%, HR 0.31, 95% CI 0.09-1.03, <em>P</em> = 0.021).</div></div><div><h3>Conclusion</h3><div>The primary ITT endpoint was not met, potentially related to the reduced power due to premature trial closure. The per-protocol analysis suggests a benefit from adjuvant therapy in ctDNA-positive patients, supporting ctDNA testing for adjuvant decision making in the future.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1120-1132"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival outcomes in POD1UM-303/InterAACT-2: a phase III study of retifanlimab plus carboplatin–paclitaxel in first-line advanced squamous anal cancer","authors":"S. Rao,&nbsp;E. Samalin-Scalzi,&nbsp;L. Evesque,&nbsp;M. Ben Abdelghani,&nbsp;F. Morano,&nbsp;A. Roy,&nbsp;L. Dahan,&nbsp;S. Tamberi,&nbsp;A.S. Dhadda,&nbsp;M.G. Zampino,&nbsp;N. Casanova,&nbsp;R. Guimbaud,&nbsp;A. Lievre,&nbsp;J. Maurel,&nbsp;P. Zhang,&nbsp;M.C. Munteanu,&nbsp;M. Jones,&nbsp;C. de la Fouchardiere,&nbsp;A. Takashima,&nbsp;M. Fakih,&nbsp;J. Spano","doi":"10.1016/j.annonc.2026.04.016","DOIUrl":"10.1016/j.annonc.2026.04.016","url":null,"abstract":"<div><h3>Background</h3><div>In the primary analysis of the POD1UM-303/InterAACT 2 trial, median progression-free survival (PFS) was significantly longer with retifanlimab plus carboplatin–paclitaxel than with placebo plus carboplatin–paclitaxel in adult, systemic treatment-naïve patients with advanced/metastatic squamous cell carcinoma of the anal canal (SCAC). In this article, the final overall survival (OS) data from PODIUM-303/InterAACT 2, along with subgroup and exploratory analyses, are presented.</div></div><div><h3>Patients and methods</h3><div>POD1UM-303/InterAACT-2 was a phase III, randomized, double-blind, controlled, multicenter trial with an optional crossover period undertaken in Europe, Australia, Japan, the UK, and the United States. The primary endpoint was PFS, and OS was the key secondary endpoint. Other endpoints included response, safety, and exploratory subgroup analyses.</div></div><div><h3>Results</h3><div>A total of 308 patients were randomly assigned (<em>n</em> = 154 for each of the retifanlimab plus carboplatin–paclitaxel and placebo plus carboplatin–paclitaxel groups), and 77 patients in the placebo plus carboplatin–paclitaxel group crossed over to receive retifanlimab monotherapy. When retifanlimab plus carboplatin–paclitaxel was compared with placebo plus carboplatin–paclitaxel in the updated efficacy analysis, there was a continued PFS benefit [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.47-0.81, nominal <em>P</em> = 0.0002] and a consistent and clinically meaningful improvement in OS (HR 0.75, 95% CI 0.55-1.01, <em>P</em> = 0.0305); median OS was 32.8 versus 22.2 months. Overall response rate was 56.5% versus 44.8%, and disease control rates were 87.7% versus 80.5%. The results of the crossover-adjusted analysis were consistent with the main analysis, and there was a consistent OS benefit in favor of retifanlimab plus carboplatin–paclitaxel in all subgroups analyzed. No new safety signals or trends were reported.</div></div><div><h3>Conclusion</h3><div>This final analysis confirms the benefits of retifanlimab plus chemotherapy in SCAC. The results suggest that retifanlimab represents a new reference treatment and standard of care for patients with inoperable, locally recurrent, or metastatic SCAC.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1157-1166"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TROP2-directed antibody-drug conjugates: new first-line treatment for all patients with advanced triple-negative breast cancer?","authors":"A.C. Garrido-Castro","doi":"10.1016/j.annonc.2026.06.015","DOIUrl":"10.1016/j.annonc.2026.06.015","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1015-1020"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148325732","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":"Overall survival according to COVID-19 mRNA vaccination co-exposure in patients treated with PD-(L)1 inhibitors: a French real-world cohort study","authors":"H. Jourdain,&nbsp;N. Haddy,&nbsp;A. Singier,&nbsp;T. Duchemin,&nbsp;L. Semenzato,&nbsp;A. Weill,&nbsp;A. Rachas,&nbsp;S. Vignot,&nbsp;M. Zureik","doi":"10.1016/j.annonc.2026.05.002","DOIUrl":"10.1016/j.annonc.2026.05.002","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1186-1190"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969950","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 randomised study of encorafenib, cetuximab, and FOLFIRI versus FOLFIRI with or without bevacizumab in BRAF V600E-mutant colorectal cancer: BREAKWATER Cohort 3","authors":"S. Kopetz,&nbsp;J. Tabernero,&nbsp;S. Lonardi,&nbsp;L. Shen,&nbsp;H.S. Wasan,&nbsp;T. Yoshino,&nbsp;E. Van Cutsem,&nbsp;T.W. Kim,&nbsp;C. Eng,&nbsp;F. Ciardiello,&nbsp;J. Desai,&nbsp;T.S. Maughan,&nbsp;R. Yaeger,&nbsp;T. Usari,&nbsp;Xiaoxi Zhang,&nbsp;E. Beyzarov,&nbsp;A. Mori,&nbsp;E. Whalley,&nbsp;Xiaosong Zhang,&nbsp;E. Elez","doi":"10.1016/j.annonc.2026.04.017","DOIUrl":"10.1016/j.annonc.2026.04.017","url":null,"abstract":"<div><h3>Background</h3><div>Encorafenib + cetuximab (EC) and mFOLFOX6 or irinotecan, leucovorin, and fluorouracil (FOLFIRI) is approved in several countries for <em>BRAF</em> V600E-mutant metastatic colorectal cancer (mCRC) based on results from the BREAKWATER trial.</div></div><div><h3>Patients and methods</h3><div>In BREAKWATER Cohort 3, eligible patients with previously untreated <em>BRAF</em> V600E-mutant mCRC were randomly assigned 1:1 to receive EC+FOLFIRI or FOLFIRI with or without bevacizumab (control). The primary endpoint was objective response rate (ORR) by blinded independent central review (BICR), and the key secondary endpoint was progression-free survival (PFS) by BICR. Other secondary endpoints included overall survival (OS) and safety.</div></div><div><h3>Results</h3><div>A total of 147 patients were randomly allocated in Cohort 3 (EC+FOLFIRI, n = 73; control, n = 74) with similar baseline demographics and disease characteristics across arms. EC+FOLFIRI demonstrated clinically meaningful and statistically significant improvement in ORR by BICR {64.4% versus 39.2%, odds ratio = 2.756 [95% confidence interval (CI) 1.420-5.348], one-sided <em>P</em>-value = 0.0011}, meeting the primary endpoint (1 March 2025, data cutoff). At the 6 January 2026 data cutoff, the key secondary endpoint was met, with EC+FOLFIRI demonstrating a clinically meaningful and statistically significant PFS [hazard ratio = 0.44 (95% CI 0.27-0.70), one-sided <em>P</em>-value = 0.0002, 15.2 versus 8.3 months]. Prolonged OS was also observed with EC+FOLFIRI (hazard ratio = 0.56 [95% CI 0.34-0.94], not estimable versus 20.3 months). Serious adverse event rates were 49.3% versus 44.1% for the EC+FOLFIRI versus control arms, respectively. The safety profile was consistent with that known for each agent.</div></div><div><h3>Conclusions</h3><div>EC+FOLFIRI demonstrated clinically meaningful and statistically significant improvements in ORR and PFS, with prolonged OS versus control in <em>BRAF</em> V600E-mutant mCRC. The safety profile was generally manageable, with no new safety signals. These data support EC+FOLFIRI as an additional new standard of care for patients with <em>BRAF</em> V600E-mutant mCRC, enabling treatment personalisation.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1133-1143"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Datopotamab deruxtecan (Dato-DXd) in combination with durvalumab as first-line treatment for unresectable locally advanced or metastatic triple-negative breast cancer: results from arms 7 and 8 of the phase Ib/II BEGONIA study","authors":"P. Schmid,&nbsp;H.-C. Wang,&nbsp;F. Lynce,&nbsp;J. Asselah,&nbsp;K.H. Jung,&nbsp;C.X. Ma,&nbsp;Y.H. Park,&nbsp;S.-C. Chen,&nbsp;P.J. Wysocki,&nbsp;R.D. Baird,&nbsp;Z. Nowecki,&nbsp;R. Fernandes,&nbsp;J. O’Shaughnessy,&nbsp;S. Lord,&nbsp;M.-F. Hou,&nbsp;L.-M. Tseng,&nbsp;C. Prady,&nbsp;P. Rao-Melacini,&nbsp;R. Stewart,&nbsp;K. Warzyszyńska,&nbsp;S.-A. Im","doi":"10.1016/j.annonc.2026.05.693","DOIUrl":"10.1016/j.annonc.2026.05.693","url":null,"abstract":"<div><h3>Background</h3><div>BEGONIA (NCT03742102) is a phase Ib/II, Simon’s 2-stage, open-label, platform study evaluating the safety and efficacy of durvalumab, an anti-programmed death ligand-1 (PD-L1) antibody, combined with novel therapies, as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). Arms 7 and 8 of BEGONIA assessed the combination of datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate, with durvalumab.</div></div><div><h3>Patients and methods</h3><div>Arm 7 included patients regardless of tumor PD-L1 expression level. Arm 8 then enrolled patients with PD-L1-high tumors, as determined by local immunohistochemistry-based testing. In Arms 7 and 8, patients received Dato-DXd 6 mg/kg intravenously plus durvalumab 1120 mg intravenously every 3 weeks. Primary endpoints were safety and tolerability, and investigator-assessed confirmed objective response rate (cORR). Secondary endpoints included cORR (Part 1), duration of response (DoR), progression-free survival (PFS) per RECIST 1.1 and overall survival (OS).</div></div><div><h3>Results</h3><div>Overall, 62 and 33 patients had received Dato-DXd and durvalumab in Arms 7 and 8, respectively. At data cutoff (29 November 2024), median study follow-up was 35.0 and 10.7 months in Arms 7 and 8, respectively. In Arm 7, cORR was 79.0% [95% confidence interval (CI) 66.8-88.3], median DoR was 17.6 months (95% CI 10.5-27.3), median PFS was 14.0 months (11.0-21.1) and median OS was not reached. In Arm 8, cORR was 81.8% (95% CI 64.5-93.0). The median DoR and median PFS for Arm 8 were immature given the short median follow-up (8.3 months in censored patients). The safety profile of the combination was manageable, with no new safety signals versus prior studies.</div></div><div><h3>Conclusions</h3><div>First-line Dato-DXd plus durvalumab demonstrated substantial and durable antitumor activity in locally advanced unresectable or metastatic TNBC, regardless of PD-L1 status.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1081-1092"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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,&nbsp;Z. Shao,&nbsp;P. Schmid,&nbsp;J. Cortes,&nbsp;D.W. Cescon,&nbsp;S. Saji,&nbsp;K.H. Jung,&nbsp;T. Bachelot,&nbsp;S. Wang,&nbsp;E.M. Ramírez,&nbsp;G. Basaran,&nbsp;A. Stradella,&nbsp;R. Mathiba,&nbsp;S.-C. Chen,&nbsp;K. Shen,&nbsp;Á. Wéber,&nbsp;N. Battelli,&nbsp;N. Niikura,&nbsp;T. Luo,&nbsp;Y.S. Chae,&nbsp;Kimberly Strickland","doi":"10.1016/j.annonc.2026.03.008","DOIUrl":"10.1016/j.annonc.2026.03.008","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Patients and methods</h3><div>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 randomly assigned 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 RECIST 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.</div></div><div><h3>Results</h3><div>Between 16 May 2022 and 11 June 2024, 644 patients were randomly assigned to receive Dato-DXd (<em>n</em> = 323) or chemotherapy (<em>n</em> = 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); <em>P</em> &lt; 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); <em>P</em> = 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 8","pages":"Pages 1066-1080"},"PeriodicalIF":80.4,"publicationDate":"2026-08-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}