ESMO Open最新文献

{"title":"The association of high body mass index with the safety and efficacy of sacituzumab govitecan in patients with metastatic triple-negative breast cancer from the ASCENT study","authors":"L. García-Estévez ,&nbsp;A. Bardia ,&nbsp;H.S. Rugo ,&nbsp;L.A. Carey ,&nbsp;V.C. Diéras ,&nbsp;S. Loibl ,&nbsp;M. Piccart ,&nbsp;L. Gianni ,&nbsp;K. Kalinsky ,&nbsp;J. O’Shaughnessy ,&nbsp;S.A. Hurvitz ,&nbsp;E. Harting ,&nbsp;T. Valdez ,&nbsp;S. Phan ,&nbsp;C. Lai ,&nbsp;J. Cortés","doi":"10.1016/j.esmoop.2025.105294","DOIUrl":"10.1016/j.esmoop.2025.105294","url":null,"abstract":"<div><h3>Background</h3><div>Sacituzumab govitecan (SG) is a trophoblast cell-surface antigen 2-directed antibody–drug conjugate (ADC) approved in multiple countries for relapsed/refractory metastatic triple-negative breast cancer (mTNBC) based on results from the phase III ASCENT study. The incidence of obesity has grown to epidemic proportions in recent decades; it is unclear what impact this has on treatment outcomes, especially for ADCs like SG that have weight-based dosing. We report the association of body mass index (BMI) with efficacy and safety of SG versus chemotherapy among patients with mTNBC from the ASCENT study.</div></div><div><h3>Patients and methods</h3><div>This <em>ad hoc</em> subgroup analysis included patients from the intent-to-treat population of ASCENT who received SG at 10 mg/kg of body weight or chemotherapy. BMI, assessed at baseline, was classified as normal (18.5 to &lt;25 kg/m²), overweight (25 to &lt;30 kg/m²), and obese (≥30 kg/m²).</div></div><div><h3>Results</h3><div>A total of 509 patients were included. Longer progression-free survival was observed with SG versus chemotherapy in patients from all BMI subgroups [normal: 4.2 versus 2.1 months, hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.34-0.67, <em>P</em> &lt; 0.0001; overweight: 4.6 versus 1.5 months, HR 0.31, 95% CI 0.20-0.47, <em>P</em> &lt; 0.0001; obese: 5.9 versus 2.6 months, HR 0.34, 95% CI 0.21-0.53, <em>P</em> &lt; 0.0001]. SG also led to improved overall survival and objective response rates versus chemotherapy in all evaluated BMI subgroups. With SG treatment, the incidence of treatment-emergent adverse events of grade ≥3, and those leading to dose reductions and study drug interruptions, was higher in patients with overweight and obese BMI compared with normal BMI; however, the rates of treatment discontinuation remained low and similar across the subgroups.</div></div><div><h3>Conclusions</h3><div>To our knowledge, this is the first study evaluating the association of BMI with outcomes with ADCs. SG demonstrated improved efficacy versus chemotherapy and a manageable safety profile in all evaluated BMI subgroups from ASCENT.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105294"},"PeriodicalIF":7.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes of tumor-agnostic targeting of BRAF, tumor mutation burden-high, and RET","authors":"A. Ronaghy ,&nbsp;E. Crimini ,&nbsp;V.R. Holla ,&nbsp;K.R. Mills Shaw ,&nbsp;A.M. Doefler ,&nbsp;E. Campbell ,&nbsp;R.K. Yang ,&nbsp;J.B. Iorgulescu ,&nbsp;K.P. Patel ,&nbsp;D.D. McPherson ,&nbsp;J. Ning ,&nbsp;F. Meric-Bernstam ,&nbsp;D.D. Karp","doi":"10.1016/j.esmoop.2025.105061","DOIUrl":"10.1016/j.esmoop.2025.105061","url":null,"abstract":"<div><h3>Background</h3><div>We report the BRAF p.V600E (BRAF V600E) mutations, high tumor mutational burden (TMB-H), and RET fusions frequency/outcomes with genomically matched therapies (GMTs). To raise awareness about GMTs providing data from a real-world scenario, the KISMET project was created. In this article we report the characteristics and the outcomes of patients with advanced cancer harboring three different classes of molecular alterations: BRAF V600E mutations, TMB-H, and RET fusions.</div></div><div><h3>Patients and methods</h3><div>We retrospectively assessed the prevalence of the three aforementioned agnostic targets among 10 893 patients who underwent next-generation sequencing (NGS) from February 2020 to May 2022. We evaluated the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) for GMT versus non-GMT in the three cohorts of patients with each specific alteration.</div></div><div><h3>Results</h3><div>BRAF V600E occurred in 6.5% (662/10 158) of patients, TMB-H in 11.2% (265/2369), and <em>RET</em> fusions in 0.6% (42/7105). GMT was given to 115 (72.3%) out of the 159 patients who started a new line of treatment after NGS testing: 65 of 85 with BRAF V600E mutations, 42 of 65 for TMB-H, and 8 of 9 for <em>RET</em> fusions. The ORR of GMT versus non-GMT was 55.6% versus 12.8% for all patients (<em>P</em> &lt; 0.0001), 51% versus 17.6% for the BRAF V600E (<em>P</em> = 0.016), 57.6% versus 9.5% for the TMB-H (<em>P</em> = 0.004), and 75% versus 0% for <em>RET</em> fusions (<em>P</em> = 0.30). The mPFS for GMT versus non-GMT was 9.6 versus 3.7 months (<em>P</em> = 0.001), 9.2 versus 4.2 months (<em>P</em> = 0.08) for BRAF V600E, and 7.9 versus 3.7 months (<em>P</em> = 0.04) for TMB-H, respectively. For the eight patients with <em>RET</em> fusions who received RET inhibitors, the mPFS was 15.0 months.</div></div><div><h3>Conclusions</h3><div>BRAF V600E, TMB-H, and <em>RET</em> fusion were found in a wide variety of advanced cancers. Improved oncological outcomes with tumor type-agnostic GMT support the value of integrating comprehensive NGS testing and GMT administration for the aforementioned targets.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105061"},"PeriodicalIF":7.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib for patients with previously treated advanced thymic carcinoma in real-world settings","authors":"K. Takagi ,&nbsp;G. Saito ,&nbsp;H. Tanaka ,&nbsp;S. Kubo ,&nbsp;T. Shukuya ,&nbsp;R. Tsugitomi ,&nbsp;T. Sasaki ,&nbsp;T. Oba ,&nbsp;N. Mamesaya ,&nbsp;T. Yamanaka ,&nbsp;M. Tachihara ,&nbsp;H. Gyotoku ,&nbsp;H. Nagashima ,&nbsp;M. Tamiya ,&nbsp;H. Kanemura ,&nbsp;T. Tozuka ,&nbsp;M. Furuta ,&nbsp;S. Sakata ,&nbsp;A. Mouri ,&nbsp;H. Miwa ,&nbsp;T. Suzuki","doi":"10.1016/j.esmoop.2025.105301","DOIUrl":"10.1016/j.esmoop.2025.105301","url":null,"abstract":"<div><h3>Background</h3><div>The REMORA trial demonstrated efficacy and safety of lenvatinib in patients previously treated for advanced thymic carcinoma. However, more data regarding its use in clinical practice are required.</div></div><div><h3>Methods</h3><div>This multicenter retrospective study included consecutive patients with advanced thymic carcinoma who began lenvatinib treatment between 23 March 2021 and 31 October 2022. The primary outcome was the objective response rate in the previously treated group, with threshold and expected values based on the results of the REMORA trial and trials of other key drugs. Subgroup analyses were carried out based on REMORA trial eligibility criteria or age.</div></div><div><h3>Results</h3><div>Eighty-seven patients were enrolled in the previously treated group [median age, 64 years (range 38-79 years); 56 (64%) males]. Most patients [82 (94%)] had a performance status of 0 or 1; 51 (59%) met the trial eligibility criteria. The objective response rate and the disease control rate were 30% [90% confidence interval (CI) 21.3% to 39.1%] and 93% (95% CI 84.6% to 97.2%), respectively. The median progression-free survival, time to treatment failure, and overall survival were 10.2 months (95% CI 7.0-13.2 months), 11.6 months (95% CI 6.9-17.0 months), and not reached (NR; 95% CI 18.3 months-NR), respectively. Seventy-three patients (84%) required dose reduction owing to adverse events, including hypertension (22%), proteinuria (20%), and palmar–plantar erythrodysesthesia syndrome (16%). Twenty patients (23%) discontinued lenvatinib due to adverse events, including anorexia (6%), left ventricular systolic dysfunction (2%), and fatigue or malaise (2%). Two patients (2%) died of adverse events. Trial-eligible patients had significantly longer progression-free survival than that in trial-ineligible patients (14.7 months versus 7.7 months; <em>P</em> = 0.03). The incidence of adverse events was higher in older patients.</div></div><div><h3>Conclusions</h3><div>The primary endpoint was unmet; however, lenvatinib demonstrated relatively favorable efficacy and safety in patients with previously treated thymic carcinoma, even in real-world clinical practice involving diverse populations.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105301"},"PeriodicalIF":7.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular toxicity of breast cancer treatments: from understanding to enhancing survivorship care","authors":"C. Dauccia ,&nbsp;E. Agostinetto ,&nbsp;L. Arecco ,&nbsp;S. Lobo-Martins ,&nbsp;M. Gitto ,&nbsp;A.R. Lyon ,&nbsp;T. López-Fernández ,&nbsp;S. Dent ,&nbsp;G. Casalino ,&nbsp;V. Agarwala ,&nbsp;E. de Azambuja","doi":"10.1016/j.esmoop.2025.105128","DOIUrl":"10.1016/j.esmoop.2025.105128","url":null,"abstract":"<div><div>The significant decline in breast cancer (BC) mortality, largely driven by advancements in drug development, makes survivorship an absolute priority. Adverse events induced by anticancer treatments, particularly long-term and irreversible complications, have emerged as a major concern for BC survivors. Many anticancer therapies used in BC are associated with an increased risk of cardiovascular (CV) toxicity which may lead to treatment discontinuation and negatively affect clinical outcomes including long-term survival. Moreover, the occurrence of late CV adverse events can significantly impact the quality of life of BC survivors. Timely recognition and management of CV toxicity is therefore crucial. Before the initiation of potentially cardiotoxic therapies, a careful risk–benefit evaluation should be carried out in all patients with BC. Over the past decades, the field of cardio-oncology has emerged to deal with these challenges. Importantly, a better understanding of the mechanisms underlying CV toxicity is crucial in order to improve strategies to diagnose, monitor, and treat and ideally prevent the CV events related to different cancer treatments.</div><div>In this review, we aim to provide an overview of the main CV toxicities associated with contemporary BC treatments. Moreover, we highlight the need to balance the expected benefits of anticancer therapies while preserving CV health in both the early and advanced settings.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105128"},"PeriodicalIF":7.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to letter re: Benefit from maintenance with PARP inhibitor in newly diagnosed ovarian cancer according to BRCA1/2 mutation type and site: a multicenter real-world study","authors":"C. Marchetti ,&nbsp;A. Fagotti ,&nbsp;R. Fruscio ,&nbsp;C. Cassani ,&nbsp;L. Incorvaia ,&nbsp;M.T. Perri ,&nbsp;C.M. Sassu ,&nbsp;C.A. Camnasio ,&nbsp;E. Giudice ,&nbsp;A. Minucci ,&nbsp;M. Seca ,&nbsp;E. Arbustini ,&nbsp;L. Vertechy ,&nbsp;M. De Bonis ,&nbsp;S.M. Boccia ,&nbsp;D. Giannarelli ,&nbsp;V. Salutari ,&nbsp;M. Distefano ,&nbsp;M.G. Ferrandina ,&nbsp;C. Nero ,&nbsp;D. Lorusso","doi":"10.1016/j.esmoop.2025.105289","DOIUrl":"10.1016/j.esmoop.2025.105289","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105289"},"PeriodicalIF":7.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nivolumab plus ipilimumab with chemotherapy as first-line treatment of patients with metastatic non-small-cell lung cancer: final, 6-year outcomes from CheckMate 9LA","authors":"D.P. Carbone ,&nbsp;T.-E. Ciuleanu ,&nbsp;M. Cobo ,&nbsp;M. Schenker ,&nbsp;B. Zurawski ,&nbsp;J. Menezes ,&nbsp;E. Richardet ,&nbsp;E. Felip ,&nbsp;Y. Cheng ,&nbsp;O. Juan-Vidal ,&nbsp;A. Alexandru ,&nbsp;H. Mizutani ,&nbsp;N. Reinmuth ,&nbsp;S. Lu ,&nbsp;M. Reck ,&nbsp;T. John ,&nbsp;A. Scherpereel ,&nbsp;P. De Marchi ,&nbsp;T. Aoyama ,&nbsp;P. Sathyanarayana ,&nbsp;L.G. Paz-Ares","doi":"10.1016/j.esmoop.2025.105123","DOIUrl":"10.1016/j.esmoop.2025.105123","url":null,"abstract":"<div><h3>Background</h3><div>The phase III CheckMate 9LA study demonstrated durable overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy versus chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). Here, we report final, 6-year efficacy and safety outcomes.</div></div><div><h3>Patients and methods</h3><div>Treatment-naive adults with stage IV/recurrent NSCLC and no sensitizing <em>EGFR/ALK</em> alterations were randomized to nivolumab plus ipilimumab with chemotherapy (<em>n</em> = 361) or chemotherapy (<em>n</em> = 358). Assessments included OS, progression-free survival, objective response rate, and duration of response (DOR) in all randomized patients and subgroups, and OS by select somatic mutation status (<em>KRAS</em>, <em>STK11</em>, <em>KEAP1</em>, and <em>TP53</em>).</div></div><div><h3>Results</h3><div>With 68.6 months' minimum follow-up, nivolumab plus ipilimumab with chemotherapy demonstrated continued OS benefit versus chemotherapy (hazard ratio 0.74, 95% confidence interval 0.63-0.87, 6-year OS rates 16% versus 10%), regardless of tumor programmed death ligand 1 (PD-L1) expression (PD-L1 &lt;1%, 20% versus 7%; PD-L1 ≥1%, 15% versus 10%) and histology (squamous, 14% versus 5%; non-squamous, 17% versus 12%). The 6-year DOR rate was 19% with nivolumab plus ipilimumab with chemotherapy; all patients in the chemotherapy arm were censored or stopped responding before this timepoint. Trends toward improved OS were observed with nivolumab plus ipilimumab with chemotherapy over chemotherapy regardless of <em>KRAS</em>, <em>STK11</em>, <em>KEAP1</em>, or <em>TP53</em> mutation status. No new safety signals were observed.</div></div><div><h3>Conclusions</h3><div>These final analyses demonstrate the durable, long-term OS and response benefit with first-line nivolumab plus ipilimumab with chemotherapy over chemotherapy in patients with metastatic NSCLC, regardless of tumor PD-L1 expression, histology, or select somatic mutation status, further supporting this regimen as a standard-of-care treatment option.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105123"},"PeriodicalIF":7.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to letter re: Benefit from maintenance with PARP inhibitor in newly diagnosed ovarian cancer according to BRCA1/2 mutation type and site: a multicenter real-world study","authors":"C. Marchetti ,&nbsp;A. Fagotti ,&nbsp;R. Fruscio ,&nbsp;C. Cassani ,&nbsp;L. Incorvaia ,&nbsp;M.T. Perri ,&nbsp;C.M. Sassu ,&nbsp;C.A. Camnasio ,&nbsp;E. Giudice ,&nbsp;A. Minucci ,&nbsp;M. Seca ,&nbsp;E. Arbustini ,&nbsp;L. Vertechy ,&nbsp;M. De Bonis ,&nbsp;S.M. Boccia ,&nbsp;D. Giannarelli ,&nbsp;V. Salutari ,&nbsp;M. Distefano ,&nbsp;M.G. Ferrandina ,&nbsp;C. Nero ,&nbsp;D. Lorusso","doi":"10.1016/j.esmoop.2025.105299","DOIUrl":"10.1016/j.esmoop.2025.105299","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105299"},"PeriodicalIF":7.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter re: Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR+/HER2− metastatic breast cancer in the US real-world setting","authors":"E. Sertesen Camoz,&nbsp;I.D. Onur,&nbsp;F. Yildiz","doi":"10.1016/j.esmoop.2025.105296","DOIUrl":"10.1016/j.esmoop.2025.105296","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105296"},"PeriodicalIF":7.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter Re: Benefit from maintenance with PARP inhibitor in newly diagnosed ovarian cancer according To BRCA1/2 mutation type and site: a multicenter real-world study","authors":"A.H. Önder,&nbsp;M.M. Çatlı","doi":"10.1016/j.esmoop.2025.105298","DOIUrl":"10.1016/j.esmoop.2025.105298","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105298"},"PeriodicalIF":7.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter re: Benefit from maintenance with PARP inhibitor in newly diagnosed ovarian cancer according to BRCA1/2 mutation type and site: a multicenter real-world study","authors":"J.H. Kim ,&nbsp;M.C. Lim","doi":"10.1016/j.esmoop.2025.105288","DOIUrl":"10.1016/j.esmoop.2025.105288","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105288"},"PeriodicalIF":7.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}