ESMO Open最新文献

{"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}

{"title":"Comparative profiling of surgically resected primary tumors and their lymph node metastases in small-cell lung cancer","authors":"K. Csende ,&nbsp;B. Ferencz ,&nbsp;K. Boettiger ,&nbsp;M.D. Pozonec ,&nbsp;A. Lantos ,&nbsp;A. Ferenczy ,&nbsp;O. Pipek ,&nbsp;A. Solta ,&nbsp;B. Ernhofer ,&nbsp;V. Laszlo ,&nbsp;E. Megyesfalvi ,&nbsp;K. Schelch ,&nbsp;V. Pozonec ,&nbsp;J. Skarda ,&nbsp;V. Skopelidou ,&nbsp;Z. Lohinai ,&nbsp;C. Lang ,&nbsp;L. Horvath ,&nbsp;K. Dezso ,&nbsp;J. Fillinger ,&nbsp;Z. Megyesfalvi","doi":"10.1016/j.esmoop.2025.104514","DOIUrl":"10.1016/j.esmoop.2025.104514","url":null,"abstract":"<div><h3>Background</h3><div>Profiling studies in small-cell lung cancer (SCLC) have mainly focused on primary tumors, omitting the potential molecular changes that might occur during lymphatic metastasis formation. Here, we assessed the molecular discordance between primary SCLCs and corresponding lymph node (LN) metastases in the light of subtype distribution and expression of clinically relevant proteins.</div></div><div><h3>Methods</h3><div>Comparative profiling of 32 surgically resected primary SCLCs and their LN metastases was achieved by RNA expression analysis and immunohistochemistry (IHC). In addition to subtype markers (ASCL1, NEUROD1, POU2F3, and YAP1), the expression of nine cancer-specific proteins was evaluated.</div></div><div><h3>Results</h3><div>The selected clinically relevant molecules showed no significant differences in their RNA expression profile when assessing the primary tumors and their corresponding LN metastases. Nevertheless, IHC analyses revealed significantly higher DLL3 expression in the primary tumors than in the LN metastases (<em>P</em> = 0.008). In contrast, NEUROD1 expression was significantly lower in the primary tumors (versus LN metastases, <em>P</em> &lt; 0.001). No statistically significant difference was found by IHC analysis in the case of other clinically relevant proteins. Concerning SCLC molecular subtypes, a change in subtype distribution was detected in 21 cases. Phenotype switching from neuroendocrine (NE) subtypes toward non-NE lesions and from non-NE landscape toward NE subtypes were both detected.</div></div><div><h3>Conclusions</h3><div>Although the molecular landscape of SCLC LN metastases largely resembles that of the tumor of origin, key differences exist in terms of DLL3 and NEUROD1 expression, and in subtype distribution. These diagnostic pitfalls should be considered when establishing the tumors’ molecular profile for future clinical trials solely based on LN biopsies.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104514"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643056","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":"Response to letter re: Anti-IL-6R Ab tocilizumab to treat paraneoplastic inflammatory syndrome of solid cancers","authors":"J.-Y. Blay ,&nbsp;M. Brahmi ,&nbsp;A. Dufresne ,&nbsp;P. Heudel","doi":"10.1016/j.esmoop.2025.104531","DOIUrl":"10.1016/j.esmoop.2025.104531","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104531"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643057","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":"The impact of co-occurring tumor suppressor mutations with mEGFR as early indicators of relapse in lung cancer","authors":"S. Hait ,&nbsp;V. Noronha ,&nbsp;A. Chowdhury ,&nbsp;A. Chaudhary ,&nbsp;B. Bawaskar ,&nbsp;G. Dahimbekar ,&nbsp;S. Ahmad ,&nbsp;A. Joshi ,&nbsp;V. Patil ,&nbsp;N. Menon ,&nbsp;M. Shah ,&nbsp;R. Kaushal ,&nbsp;A. Choughule ,&nbsp;A. Bharde ,&nbsp;J. Khandare ,&nbsp;G. Shafi ,&nbsp;D. Lakhwani ,&nbsp;S. Desai ,&nbsp;P. Chandrani ,&nbsp;K. Prabhash ,&nbsp;A. Dutt","doi":"10.1016/j.esmoop.2025.104479","DOIUrl":"10.1016/j.esmoop.2025.104479","url":null,"abstract":"<div><h3>Background</h3><div>Lung adenocarcinoma frequently presents with <em>EGFR</em> mutations, often progressing on <em>EGFR</em> tyrosine kinase inhibitors (TKIs) despite an initial response. Progression is frequently driven by additional genetic changes, including mutations in tumor suppressor genes (TSGs). Understanding the role of these concurrent TSG mutations can help elucidate resistance mechanisms and guide the development of more effective treatment approaches.</div></div><div><h3>Materials and methods</h3><div>We examined survival outcomes in 483 <em>EGFR</em>-mutant (m<em>EGFR</em>) patients from the GENIE BPC non-small-cell lung cancer (NSCLC) dataset. To understand the mutational landscape and clonal dynamics, whole exome sequencing (WES) was carried out on 48 tumor samples from 16 m<em>EGFR</em> patients at both baseline and post-relapse. A comprehensive gene panel was applied to 200 liquid biopsy samples obtained longitudinally from 25 patients to track clonal evolution.</div></div><div><h3>Results</h3><div>m<em>EGFR</em> patients with co-occurring TSG mutations exhibited significantly worse outcomes. In the GENIE dataset, overall survival (OS) was shorter [51.11 versus 99.3 months; hazard ratio (HR) 1.8, confidence interval (CI) 1.22-2.75, <em>P</em> = 0.003] and progression-free survival (PFS) was reduced (9.83 versus 11.48 months; HR 1.4, CI 1.03-1.91, <em>P</em> = 0.026). WES analysis revealed 17 TSG mutations that were retained and showed clonal enrichment, particularly in early relapse (progression within 10 months of TKI initiation) or intermediate-stage relapse (relapse occurred between 10 and 20 months), indicated by increased variant allele frequency and their presence was strongly linked to early relapse. Longitudinal clonal studies further confirmed that TSG mutations co-occurring with m<em>EGFR</em> were often truncal, predominantly in early relapsers. Survival analysis using this subset of 17 TSGs showed significantly shorter OS (55.26 versus 99.3 months; HR 1.7, CI 1.12-2.65, <em>P</em> = 0.011) and PFS (9.67 versus 13.12 months; HR 1.5, CI 1.08-2.10, <em>P</em> = 0.013).</div></div><div><h3>Conclusions</h3><div>A set of 17 co-occurring TSG mutations has been identified as key biomarkers for early relapse in m<em>EGFR</em> lung adenocarcinoma. Longitudinal genomic monitoring, with a focus on clonal evolution, offers valuable insights that can inform personalized treatment strategies and potentially improve patient outcomes.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104479"},"PeriodicalIF":7.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621288","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":"Response to: The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP)","authors":"D.T. Rieke ,&nbsp;R. Kurzrock","doi":"10.1016/j.esmoop.2025.104516","DOIUrl":"10.1016/j.esmoop.2025.104516","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104516"},"PeriodicalIF":7.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621284","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":"Multimodality immunotherapy with avelumab, short-course radiotherapy, and cyclophosphamide in head and neck cancer: the CONFRONT phase I-II trial","authors":"M.C. Merlano ,&nbsp;N. Denaro ,&nbsp;M. Paccagnella ,&nbsp;A. Abbona ,&nbsp;D. Galizia ,&nbsp;S. Alfieri ,&nbsp;C. Bergamini ,&nbsp;E. Orlandi ,&nbsp;A.M. Merlotti ,&nbsp;S. Bondi ,&nbsp;L. Licitra ,&nbsp;O. Garrone","doi":"10.1016/j.esmoop.2025.104498","DOIUrl":"10.1016/j.esmoop.2025.104498","url":null,"abstract":"<div><h3>Background</h3><div>Inhibition of the programmed cell death protein 1–programmed death-ligand 1 (PD-1–PD-L1) axis results in a modest objective response rate (ORR) in recurrent/metastatic head and neck squamous cell carcinoma. This study aimed to evaluate whether the addition of metronomic chemotherapy and a single fraction of radiotherapy could synergistically operate with anti-PD-L1 treatment.</div></div><div><h3>Patients and methods</h3><div>We conducted a phase I-II study evaluating avelumab (10 mg/kg intravenously every 2 weeks), low-dose cyclophosphamide (50 mg/day, fixed dose, without treatment breaks), and a single fraction of radiotherapy (8 Gy) to one lesion. The phase II portion of the study followed Simon’s two-stage optimal design. A total of 6 patients were enrolled in phase I, and 20 patients were accrued and analyzed in phase II before determining progression to the second stage (51 patients). The primary endpoint was ORR. Further, a panel of circulating cytokines was analyzed to explore potential toxicity and/or efficacy markers.</div></div><div><h3>Results</h3><div>Between January 2019 and June 2020, 20 patients were enrolled. In phase I, only one dose-limiting toxicity was observed among the six patients, allowing progression to phase II. At the end of stage I, five objective responses (2 complete responses and 3 partial responses) were recorded, failing to meet the threshold of six responses required to reject the null hypothesis. The median progression-free survival and overall survival were 3.0 and 9.2 months, respectively. Treatment was well tolerated. Low baseline levels of transforming growth factor-beta (TGF-β) and/or interleukin (IL)-4 were associated with a higher risk of immune-related adverse events (irAEs), whereas high baseline levels of IL-6 and vascular endothelial growth factor (VEGF) correlated with poor outcomes.</div></div><div><h3>Conclusions</h3><div>Our results did not achieve the ORR threshold required to reject the null hypothesis in this cohort of unselected patients with relapsed/metastatic head and neck cancer. IL-6 and VEGF were associated with overall survival, whereas TGF-β and IL-4 correlated with irAEs.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104498"},"PeriodicalIF":7.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621285","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":"The role of physical activity, sedentary behaviour, diet, adiposity and body composition on health-related quality of life and cancer-related fatigue after diagnosis of colorectal cancer: a Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis","authors":"G. Markozannes ,&nbsp;S. Cividini ,&nbsp;D. Aune ,&nbsp;N. Becerra-Tomás ,&nbsp;S. Kiss ,&nbsp;K. Balducci ,&nbsp;R. Vieira ,&nbsp;M. Cariolou ,&nbsp;A. Jayedi ,&nbsp;D.C. Greenwood ,&nbsp;N.T. Brockton ,&nbsp;H. Croker ,&nbsp;P. Mitrou ,&nbsp;E. Copson ,&nbsp;A.G. Renehan ,&nbsp;M. Bours ,&nbsp;W. Demark-Wahnefried ,&nbsp;M.M. Hudson ,&nbsp;A.M. May ,&nbsp;F.T. Odedina ,&nbsp;D.S.M. Chan","doi":"10.1016/j.esmoop.2025.104301","DOIUrl":"10.1016/j.esmoop.2025.104301","url":null,"abstract":"<div><h3>Background</h3><div>The impact of physical activity, sedentary behaviour, diet, adiposity, and body composition on health-related quality of life (HRQoL) and cancer-related fatigue among colorectal cancer survivors remains uncertain.</div></div><div><h3>Methods</h3><div>PubMed, Embase, and CENTRAL were systematically searched until April 2023 for relevant randomised controlled trials (RCTs) and cohort studies. Random-effects meta-analyses or descriptive syntheses were conducted depending on the number of studies. The evidence was interpreted and graded by an independent World Cancer Research Fund Expert Committee and Expert Panel.</div></div><div><h3>Results</h3><div>We included 31 RCTs (18 exercise, 14 diet) and 30 cohort studies (8 physical activity, 3 sedentary behaviour, 13 diet, 9 adiposity and body composition). Meta-analyses were possible for exercise RCTs that showed non-significant effects but indicative of improved HRQoL (overall four trials for global HRQoL, physical and emotional well-being) and fatigue (five trials). These studies were rated at a high risk of bias (RoB), and evidence was graded as ‘very low certainty of an effect’. Descriptive synthesis of interventions to improve diet quality suggested small improvements in global HRQoL and physical well-being, but with a high RoB rating leading to a ‘low certainty’ grading. Evidence from RCTs on probiotics and supplements and evidence from observational studies on sedentary behaviour, and various dietary and body composition factors was generally inconsistent and too scarce to draw conclusions.</div></div><div><h3>Conclusions</h3><div>Exercise and diet quality interventions might improve HRQoL and fatigue outcomes in colorectal cancer survivors. The evidence overall was limited and should be strengthened by larger, well-designed RCTs across the cancer continuum.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104301"},"PeriodicalIF":7.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621287","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":"89P Duchenne muscular dystrophy gene product expression is associated with survival in sarcoma","authors":"S. Divakar ,&nbsp;L. El-Khoury ,&nbsp;K. Anthony ,&nbsp;L.J. Machado","doi":"10.1016/j.esmoop.2025.104402","DOIUrl":"10.1016/j.esmoop.2025.104402","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104402"},"PeriodicalIF":7.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679082","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":"84P Exploring BET inhibitors as promising agents for solitary fibrous tumor","authors":"J.L. Mondaza-Hernandez ,&nbsp;Y. Li ,&nbsp;P. Romero-Gonzalez ,&nbsp;J. Lopez ,&nbsp;J.T. Nguyen ,&nbsp;D. Da Silva Moura ,&nbsp;H.N. Hayenga ,&nbsp;L. Bleris ,&nbsp;J. Martin-Broto","doi":"10.1016/j.esmoop.2025.104397","DOIUrl":"10.1016/j.esmoop.2025.104397","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104397"},"PeriodicalIF":7.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679248","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":"16P Survival outcomes and predictors in chromophobe renal cell carcinoma (ChRCC): A machine learning analysis","authors":"N. Almasri ,&nbsp;S.A. Alshwayyat ,&nbsp;T.A. Alshwayyat ,&nbsp;M. Alshwayyat ,&nbsp;J. Abu-Khass ,&nbsp;A. Alenezy","doi":"10.1016/j.esmoop.2025.104324","DOIUrl":"10.1016/j.esmoop.2025.104324","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104324"},"PeriodicalIF":7.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679352","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}