ESMO Open最新文献

{"title":"Detection of minimal residual disease and prediction of recurrence in breast cancer using a plasma-only circulating tumor DNA assay","authors":"W. Janni ,&nbsp;B. Rack ,&nbsp;T.W.P. Friedl ,&nbsp;A.D. Hartkopf ,&nbsp;L. Wiesmüller ,&nbsp;K. Pfister ,&nbsp;F. Mergel ,&nbsp;A. Fink ,&nbsp;T. Braun ,&nbsp;F. Mehmeti ,&nbsp;N. Uhl ,&nbsp;A. De Gregorio ,&nbsp;J. Huober ,&nbsp;T. Fehm ,&nbsp;V. Müller ,&nbsp;T.A. Rich ,&nbsp;D.J. Dustin ,&nbsp;S. Zhang ,&nbsp;S.T. Huesmann","doi":"10.1016/j.esmoop.2025.104296","DOIUrl":"10.1016/j.esmoop.2025.104296","url":null,"abstract":"<div><h3>Background</h3><div>Detection of minimal residual disease (MRD) in early breast cancer (EBC) after curative-intent treatment may identify patients at risk for recurrence. Most circulating tumor DNA (ctDNA)-based MRD assays require knowledge of genomic alterations from tumor tissue. However, tissue availability may be limited in some patients. Here, we evaluated sensitivity and specificity for recurrence detection, using a plasma-only ctDNA MRD assay.</div></div><div><h3>Materials and methods</h3><div>For this pilot study, 47 plasma samples from 38 EBC patients were collected at 12 or 36 months post-diagnosis or at clinical recurrence. ctDNA presence was determined by a custom bioinformatics classifier that identifies tumor-derived somatic variants and methylation profiles specific to individual cancer types using a 5-Mb next-generation sequencing panel.</div></div><div><h3>Results</h3><div>ctDNA was detected at or before distant recurrence in 11/14 (79%) patients [sensitivity was 85% (11/13) among samples collected within 2 years from recurrence]. Lead time was evaluable in 4/6 (67%) samples collected before distant recurrence with detectable ctDNA and ranged from 3.4 to 18.5 months. ctDNA was not detected in samples from patients without recurrence (<em>n</em> = 13).</div></div><div><h3>Conclusions</h3><div>This study demonstrates the feasibility of MRD detection in EBC using a plasma-only multiomic ctDNA-based approach. Larger studies are ongoing to further validate the clinical performance of the assay and demonstrate its applications.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104296"},"PeriodicalIF":7.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global health inequalities in female-specific cancers from 1990 to 2021: insights from the Global Burden of Disease Study 2021","authors":"X. Shu ,&nbsp;Y. Meng ,&nbsp;J. Yang ,&nbsp;S. Cui ,&nbsp;F. Kong","doi":"10.1016/j.esmoop.2025.104512","DOIUrl":"10.1016/j.esmoop.2025.104512","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104512"},"PeriodicalIF":7.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authors response to Letter re: The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP) molecular complexity and response to targeted therapy","authors":"K. Verkerk ,&nbsp;E.E. Voest","doi":"10.1016/j.esmoop.2025.104515","DOIUrl":"10.1016/j.esmoop.2025.104515","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104515"},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How we treat patients with metastatic uveal melanoma","authors":"E.F. Saldanha ,&nbsp;M.F. Ribeiro ,&nbsp;I. Hirsch ,&nbsp;A. Spreafico,&nbsp;S.D. Saibil ,&nbsp;M.O. Butler","doi":"10.1016/j.esmoop.2025.104496","DOIUrl":"10.1016/j.esmoop.2025.104496","url":null,"abstract":"<div><div>Uveal melanoma is the most prevalent and aggressive intraocular malignancy affecting adults. Compared with cutaneous melanoma, uveal melanoma has distinct pathogenesis and molecular characteristics. Not surprisingly, it derives limited benefits from checkpoint inhibitors. Until recently, no systemic therapy had impacted survival outcomes for this patient population. Tebentafusp, a T-cell receptor-based molecule, is the first US Food and Drug Administration/European Medicines Agency-approved systemic therapy to improve the survival outcomes for uveal melanoma patients expressing HLA-A∗02:01. Only 45%-50% of this patient population will express the HLA-A∗02:01, however, and therefore are eligible to receive this novel treatment. Moreover, global access to tebentafusp is limited, and there are no guidelines to aid clinicians in decision-making regarding treatment. In this review, we outline our experience as Canada's largest tertiary referral centre in managing metastatic uveal melanoma patients and provide a comprehensive overview of the currently available treatment options, challenging scenarios, and ongoing clinical trials for patients with metastatic uveal melanoma.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104496"},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17)”","authors":"E.J. Kang ,&nbsp;Y. Yang ,&nbsp;S. Lee ,&nbsp;Y.J. Kim ,&nbsp;S.M. Lim ,&nbsp;M.-J. Ahn ,&nbsp;Y.J. Choi ,&nbsp;Y. Lee ,&nbsp;T.M. Kim ,&nbsp;I. Kim ,&nbsp;H.K. Ahn ,&nbsp;H.-C. Jeung ,&nbsp;S.I. Lee ,&nbsp;S.Y. Oh ,&nbsp;W.K. Bae ,&nbsp;H. Ryu ,&nbsp;K.H. Park ,&nbsp;K.H. Lee","doi":"10.1016/j.esmoop.2025.104302","DOIUrl":"10.1016/j.esmoop.2025.104302","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104302"},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular tumour board in gastrointestinal cancers","authors":"L. Boscolo Bielo ,&nbsp;E. Crimini ,&nbsp;M. Repetto ,&nbsp;M. Barberis ,&nbsp;E. Battaiotto ,&nbsp;J. Katrini ,&nbsp;E. Martino ,&nbsp;G. Gaudio ,&nbsp;M. Lombardi ,&nbsp;C. Zanzottera ,&nbsp;G. Aurilio ,&nbsp;C. Belli ,&nbsp;Y. Zhan ,&nbsp;V. Fuorivia ,&nbsp;R.M. Marsicano ,&nbsp;J.D. Etessami ,&nbsp;P. Zagami ,&nbsp;A. Marra ,&nbsp;D. Trapani ,&nbsp;B. Taurelli Salimbeni ,&nbsp;G. Curigliano","doi":"10.1016/j.esmoop.2025.104510","DOIUrl":"10.1016/j.esmoop.2025.104510","url":null,"abstract":"<div><h3>Background</h3><div>Comprehensive genomic profiling (CGP) is being increasingly adopted in clinical practice to guide the use of molecularly guided treatment options (MGTOs). To optimize the integration of MGTOs in routine cancer care, molecular tumour boards (MTBs) have been established. Limited data are available to address the clinical value of implementing MTBs to inform treatment decision making in patients with gastrointestinal (GI) cancers.</div></div><div><h3>Materials and methods</h3><div>We retrospectively retrieved medical records from patients with advanced GI cancers discussed at the European Institute of Oncology’s MTB between August 2019 and December 2024. We evaluated clinical outcomes resulting from applying MGTOs in cancer care according to MTB recommendations, describing real-world progression-free (rwPFS) and overall survival (OS), and used the growth modulation index (GMI) (ratio of PFS^MTB to PFS^prior) to quantify the effectiveness of MTB’s recommended cancer treatment in extending PFS.</div></div><div><h3>Results</h3><div>Among 192 patients with GI cancers discussed at MTB, 139 (72.3%) received an MTB treatment recommendation. For patients with available follow-up data (<em>n</em> = 82), 31 patients (41.4%, 17.7% overall) received MGTOs, while 51 patients received standard treatments. Patients receiving MGTOs exhibited a longer rwPFS compared with cases receiving standard therapies [5.35 versus 3.55 months, hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.36-1.08, <em>P =</em> 0.08] and with unmatched cases showing actionable biomarkers but not treated with targeted agents (<em>n</em> = 31) (rwPFS 5.35 versus 2.40 months, HR 0.49, 95% CI 0.27-0.90, <em>P</em> = 0.02). The use of MGTOs resulted in a GMI of 1.12 (interquartile range 0.68-2.36). The European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) tier I-III treatments resulted in a restricted mean PFS gain of 4.87 months compared with standard therapies (95% CI 1.02-8.72 months, <em>P =</em> 0.01). No OS difference was observed between patients receiving MGTOs and standard treatments (<em>P =</em> 0.89).</div></div><div><h3>Conclusions</h3><div>Our results suggest that MTB-informed clinical decision making could provide valuable clinical benefits and expanded therapeutic options in patients affected by advanced GI cancers.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104510"},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-related adverse events are associated with better event-free survival in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage triple-negative breast cancer","authors":"A. Rios-Hoyo ,&nbsp;J. Dai ,&nbsp;T. Noel ,&nbsp;K.R.M. Blenman ,&nbsp;T. Park ,&nbsp;L. Pusztai","doi":"10.1016/j.esmoop.2025.104494","DOIUrl":"10.1016/j.esmoop.2025.104494","url":null,"abstract":"<div><h3>Background</h3><div>Immune-related adverse events (irAEs) have been associated with improved outcomes in different tumors; however, their impact during neoadjuvant immune checkpoint inhibitor therapy and chemotherapy in triple-negative breast cancer (TNBC) remains unknown.</div></div><div><h3>Patients and methods</h3><div>This analysis included patients from a phase I/II single-arm clinical trial at Yale Cancer Center and its regional care centers. The study was conducted from December 2015 to December 2020. Eligible patients were adults aged ≥18 years with clinical stage I-III TNBC for whom systemic chemotherapy was indicated. Patients received durvalumab concomitant with nab-paclitaxel and dose-dense doxorubicin–cyclophosphamide. Durvalumab was not administered post-operatively. We examined the association of developing an irAE with pathologic complete response (pCR = ypT0/is, ypN0), residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS). A landmark analysis from the time of surgery was also carried out.</div></div><div><h3>Results</h3><div>A total of 67 patients were eligible for toxicity and efficacy analysis; of these, 27 had irAEs of any grade and 13 had multiple irAEs. The median follow-up was 61 months (range 6.8-94.03 months). The most frequent irAEs were dermatologic (<em>n</em> = 14), endocrine (<em>n</em> = 13), and gastrointestinal (<em>n</em> = 5). Patients who experienced irAEs achieved a pCR or RCB 0-1 rate of 56% and 73%, respectively, compared with 40% and 55% in those without irAEs (<em>P</em> = 0.309 and 0.19). Development of irAE was also associated with significantly improved EFS [hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.09-0.66, <em>P</em> = 0.024] and a trend for improved OS (HR 0.42; 95% CI 0.14-1.27, <em>P</em> = 0.17). Patients with more than one irAE had no EFS events. The landmark analysis showed similar results (EFS HR 0.19, <em>P</em> = 0.014; OS HR 0.4, <em>P</em> = 0.16).</div></div><div><h3>Conclusions</h3><div>The development of irAE was associated with numerically improved pCR rates, lower RCB, and significantly higher EFS in patients treated with neoadjuvant immune checkpoint therapy plus chemotherapy.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104494"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of palbociclib plus letrozole on patient-reported health-related quality of life: extended follow-up of the PALOMA-2 trial","authors":"N. Harbeck ,&nbsp;V. Dieras ,&nbsp;K.A. Gelmon ,&nbsp;R.S. Finn ,&nbsp;M. Martin ,&nbsp;P. Neven ,&nbsp;S. Kim ,&nbsp;J. Ma ,&nbsp;E. Gauthier ,&nbsp;E. Broughton ,&nbsp;J. Doan ,&nbsp;H.S. Rugo","doi":"10.1016/j.esmoop.2025.104497","DOIUrl":"10.1016/j.esmoop.2025.104497","url":null,"abstract":"<div><h3>Background</h3><div>Metastatic breast cancer (mBC) remains incurable, highlighting the importance of patient-reported outcomes (PROs) in treatment decision making. In the randomized phase III PALOMA-2 trial, health-related quality of life (HRQoL) was maintained in patients receiving first-line palbociclib plus letrozole compared with placebo plus letrozole after a median follow-up of 22.3 months. However, little is known about HRQoL for patients taking palbociclib for an extended period of time. Here, we report the PRO results from the PALOMA-2 trial after a median follow-up time of 90 months.</div></div><div><h3>Patients and methods</h3><div>Women with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) mBC were randomly assigned 2 : 1 to receive palbociclib plus letrozole (<em>n</em> = 444) or placebo plus letrozole (<em>n</em> = 222). HRQoL was assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) and EuroQoL five-dimensions three-level (EQ-5D-3L) questionnaires, administered on site on day 1 of cycles 1, 2, and 3 and then every other cycle from cycle 5 until study end. Treatment arm comparisons were made for change from baseline in QoL and time to deterioration in FACT-B (definitive definition, TTDD).</div></div><div><h3>Results</h3><div>After a median follow-up of 90 months, no significant differences between treatments were observed for overall change from baseline in FACT-B total, FACT-B subscales, and EQ-5D-3L scores. While TTDD did not differ between treatment arms, TTDD was shorter for patients with disease progression versus those without disease progression (hazard ratio 0.644, <em>P</em> &lt; 0.001). Individual items assessing side-effects and hair loss favored the palbociclib plus letrozole arm versus the letrozole arm; no treatment difference was observed for items assessing pain.</div></div><div><h3>Conclusions</h3><div>This extended follow-up analysis of PROs in PALOMA-2 shows continued QoL maintenance for patients with ER+/HER2− mBC receiving long-term palbociclib plus letrozole treatment.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104497"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive genomic profiling by liquid biopsy portrays metastatic colorectal cancer mutational landscape to predict antitumor efficacy of FOLFIRI plus cetuximab in the CAPRI-2 GOIM trial","authors":"D. Ciardiello ,&nbsp;L.B. Bielo ,&nbsp;S. Napolitano ,&nbsp;T.P. Latiano ,&nbsp;A. De Stefano ,&nbsp;E. Tamburini ,&nbsp;I. Toma ,&nbsp;R. Bordonaro ,&nbsp;A.E. Russo ,&nbsp;S. Pisconti ,&nbsp;C. Nisi ,&nbsp;C. Lotesoriere ,&nbsp;S. Vallarelli ,&nbsp;S. Lonardi ,&nbsp;D. Iacono ,&nbsp;C. Cremolini ,&nbsp;G. Tortora ,&nbsp;P. Tagliaferri ,&nbsp;F. Pietrantonio ,&nbsp;G. Rosati ,&nbsp;G. Martini","doi":"10.1016/j.esmoop.2025.104511","DOIUrl":"10.1016/j.esmoop.2025.104511","url":null,"abstract":"<div><h3>Background</h3><div>Limited evidence is currently available on the role of liquid biopsy (LBx) in predicting the efficacy of anti-epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer (mCRC).</div></div><div><h3>Methods</h3><div>The CAPRI-2 GOIM is a phase II trial investigating the use of LBx-comprehensive genomic profiling (CGP)-guided, cetuximab-based treatment through three subsequent lines of therapy in patients with <em>RAS/BRAF</em> wild-type (WT) mCRC. LBx-CGP is carried out at baseline and at progressive disease to first- and second-line therapies. In case of <em>RAS/BRAF</em> WT circulating tumor DNA at progressive disease, EGFR therapeutic blockade is continued by combining cetuximab with a different chemotherapy backbone. The primary endpoint is overall response rate (ORR) by RECIST 1.1 criteria. Tumor molecular characteristics by LBx-CGP are correlated with treatment efficacy.</div></div><div><h3>Results</h3><div>One hundred and ninety-two <em>RAS/BRAF</em> WT microsatellite stable mCRC patients treated with FOLFIRI plus cetuximab with baseline LBx-CGP and assessable for response were included in the analysis. One hundred and thirty-seven patients with WT tumors for potential anti-EGFR drug resistance genes <em>(RAS/BRAF/EGFR/PIK3CA/MAP2K1/MET/RET/ALK/ROS1/NTRK/NF1/FGFR</em>, and <em>HER2</em> amplification; ‘negatively hyper-selected’ cases) had 78.1% ORR compared with 54.5% ORR for patients with mutations [odds ratio 2.95, 95% confidence interval (CI) 1.44-6.10, <em>P</em> = 0.001]. ‘Negatively hyper-selected’ patients had median progression-free survival of 12.35 months (95% CI 10.58-15.4 months) compared with 8.68 months (95% CI 4.87-12.1 months) for patients with mutations (hazard ratio 0.64, 95% CI 0.44-0.92, <em>P</em> = 0.017). High cancer cell clonality of pathogenic variants (PVs) correlated with worse median progression-free survival (3.55 months, 95% CI 2.57 months to NE) compared with low cancer cell clonality of PV (9.63 months, 95% CI 7.16 months to NE, <em>P</em> = 0.21). After first-line therapy failure, approximately one out of five patients had acquired PVs of potential anti-EGFR drug resistance genes, whereas <em>RAS/BRAF</em> WT circulating tumor DNA was maintained in most patients (78.5%).</div></div><div><h3>Conclusions</h3><div>These results support the integration of LBx-CGP for implementing the efficacy and for optimizing the use of anti-EGFR therapies in <em>RAS/BRAF</em> WT mCRC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104511"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Avelumab first-line maintenance for advanced urothelial carcinoma: long-term outcomes from the JAVELIN Bladder 100 trial in older patients☆","authors":"S. Gupta ,&nbsp;M.A. Climent Duran ,&nbsp;S.S. Sridhar ,&nbsp;T. Powles ,&nbsp;J. Bellmunt ,&nbsp;S.H. Park ,&nbsp;H. Gurney ,&nbsp;N. Tsuchiya ,&nbsp;D.P. Petrylak ,&nbsp;Y. Tomita ,&nbsp;A. di Pietro ,&nbsp;J. Manitz ,&nbsp;K. Tyroller ,&nbsp;J. Hoffman ,&nbsp;N. Jacob ,&nbsp;P. Grivas","doi":"10.1016/j.esmoop.2025.104506","DOIUrl":"10.1016/j.esmoop.2025.104506","url":null,"abstract":"<div><h3>Background</h3><div>In the JAVELIN Bladder 100 phase III trial, avelumab first-line (1L) maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS) versus BSC alone in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) without progression following platinum-based chemotherapy. Older age (≥65 years) is a known risk factor for bladder cancer with a median age at diagnosis of 73.0 years. We report exploratory analyses in subgroups based on older age (≥65 years).</div></div><div><h3>Materials and methods</h3><div>Eligible patients with la/mUC without progression after 1L platinum-based chemotherapy were randomized to receive avelumab plus BSC (<em>n</em> = 350) or BSC alone (<em>n</em> = 350). This exploratory analysis included subgroups aged ≥65 years, ≥65-&lt;75 years, ≥75 years, and the subset aged ≥80 years. OS (primary endpoint) and progression-free survival (PFS) from randomization were analyzed using the Kaplan–Meier method.</div></div><div><h3>Results</h3><div>Of 700 patients, 464 (66.3%) were aged ≥65 years. Median OS with avelumab plus BSC versus BSC alone was 26.1 versus 15.5 months (hazard ratio 0.70, 95% confidence interval 0.56-0.89) in all patients aged ≥65 years and 28.7 versus 17.1, 24.0 versus 13.5, and 24.9 versus 10.0 months, respectively, in patients aged ≥65-&lt;75, ≥75, and ≥80 years. PFS analyses favored avelumab plus BSC versus BSC alone in all subgroups. No new safety concerns were identified in patients aged ≥65 years, including those treated for ≥12 months. Quality-adjusted time without symptoms or toxicity was 4.57 months longer with avelumab plus BSC versus BSC alone (a 30.35% relative improvement). Limitations include small sample size for the ≥80-year age subgroup and the exploratory design.</div></div><div><h3>Conclusions</h3><div>These exploratory analyses support the efficacy and tolerability of avelumab 1L maintenance in patients aged ≥65 years with la/mUC that has not progressed following chemotherapy, suggesting that older age should not solely prevent a patient from receiving avelumab 1L maintenance.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104506"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}