ESMO Open最新文献

{"title":"Cyclin-dependent kinase 4/6 inhibitors beyond progression in hormone receptor-positive, HER2-negative advanced breast cancer: a systematic review and meta-analysis (REIGNITE study)","authors":"L.F.C. de Almeida ,&nbsp;L.F. Leite ,&nbsp;V.O.C. Filho ,&nbsp;M.M. Noronha ,&nbsp;A.P. Cappellaro ,&nbsp;M. Gouveia ,&nbsp;J.L. da Silva ,&nbsp;B. Ernst ,&nbsp;A.C. de Melo ,&nbsp;P. Tarantino ,&nbsp;F. Batalini","doi":"10.1016/j.esmoop.2025.105808","DOIUrl":"10.1016/j.esmoop.2025.105808","url":null,"abstract":"<div><h3>Background</h3><div>Adding cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy (ET) is considered the first-line treatment of advanced HR-positive/HER2-negative breast cancer. However, with the recent approval of several additional targeted agents, the optimal treatment sequencing remains uncertain, and it is unclear whether the benefits of CDK4/6i extend beyond progression on first-line therapy.</div></div><div><h3>Materials and methods</h3><div>We conducted a systematic review and meta-analysis to evaluate the efficacy of CDK4/6i in the second-line setting after progression on CDK4/6i in the first line, with a particular focus on patients who had either <em>PIK3CA</em> or <em>ESR1</em> mutation. We included randomized clinical trials (RCTs) comparing CDK4/6i combined with ET to ET alone in patients who experienced tumor progression on CDK4/6i treatment in the first-line setting. The results were pooled using a random-effects model with 95% confidence interval (CI).</div></div><div><h3>Results</h3><div>Five RCTs encompassing 1184 patients were included. Overall, CDK4/6i plus ET significantly improved progression-free survival (PFS) versus ET alone, yielding a hazard ratio of 0.73 (95% CI 0.56-0.94, <em>P</em> &lt; 0.05), with a more prominent benefit in patients who switched the CDK4/6i (hazard ratio 0.61, 95% CI 0.48-0.77, <em>P</em> &lt; 0.05). The benefit was consistent in patients with somatic <em>PIK3CA</em> mutations (hazard ratio 0.71, 95% CI 0.52-0.98, <em>P</em> &lt; 0.05), and <em>ESR1</em> mutations (hazard ratio 0.66, 95% CI 0.49-0.89, <em>P</em> &lt; 0.05). The toxicity profile was compatible with the known side effects from CDK4/6i.</div></div><div><h3>Conclusions</h3><div>Our results support the strategy of switching the CDK4/6i in the second-line setting and demonstrate persistent benefit even in patients with <em>PIK3CA</em> or <em>ESR1</em> mutations.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105808"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211876","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: Improving chemotherapy-induced peripheral neuropathy in cancer patients using a combined qigong and self-administered acupressure intervention: a randomized controlled trial","authors":"D.S.T. Cheung","doi":"10.1016/j.esmoop.2025.105836","DOIUrl":"10.1016/j.esmoop.2025.105836","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105836"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227416","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":"Minimum standards of specialist adolescent and young adult (AYA) cancer care units: recommendations and implementation roadmap","authors":"U. Košir ,&nbsp;A. Totovina ,&nbsp;D. Stark ,&nbsp;A. Ferrari ,&nbsp;J. de Munter ,&nbsp;W.T.A. van der Graaf ,&nbsp;E. Manten-Horst ,&nbsp;K. Rizvi","doi":"10.1016/j.esmoop.2025.105829","DOIUrl":"10.1016/j.esmoop.2025.105829","url":null,"abstract":"<div><div>In 2022, according to the Global Cancer Observatory, &gt;115 000 adolescents and young adults (AYAs; aged 15-39 years) were diagnosed with cancer across Europe. Despite their unique biological and psychosocial needs, AYAs face disparity of access to specialised oncology services, particularly outside major urban centres in the east and south of Europe. Addressing these inequalities is essential to ensuring comprehensive and equitable cancer care. As part of EU4Health, the European Union Network of Youth Cancer Survivors (EU-CAYAS-NET) consortium was established to advance Europe’s Beating Cancer Plan. The project aimed to develop—with patient organisations at the helm—evidence-based recommendations to standardise and improve care across Europe, ultimately enhancing outcomes and quality of life for all young people.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105829"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205942","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":"Critical insights on real-life PD-L1 histopathological workflow and assessment in esophageal, esophagogastric junction, and gastric carcinoma in Italy","authors":"A. Gambella ,&nbsp;F. Grillo ,&nbsp;P. Parente ,&nbsp;A. Vanoli ,&nbsp;A. Caputo ,&nbsp;M. Paudice ,&nbsp;V. Angerilli ,&nbsp;F. Castri ,&nbsp;A. Pastorino ,&nbsp;M. Fassan ,&nbsp;L. Mastracci","doi":"10.1016/j.esmoop.2025.105846","DOIUrl":"10.1016/j.esmoop.2025.105846","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have improved survival in locally advanced and metastatic esophageal, esophagogastric junction, and gastric carcinoma (GEC). Patient selection for ICI-treatment relies on PD-L1 protein expression assessment via immunohistochemistry (IHC). This study aimed to evaluate the real-world assessment of PD-L1 IHC results compared with clinical trial data.</div></div><div><h3>Patients and methods</h3><div>This multicentric, real-world retrospective study analyzed PD-L1 IHC data from 28 Italian pathology centers of GEC cases diagnosed between October 2023 and September 2024. The study documented PD-L1 expression distribution via combined positive (CPS), tumor proportion (TPS), and tumor area positivity (TAP) scores, and investigated the impact of several factors on IHC results.</div></div><div><h3>Results</h3><div>We collected 1936 cases: 1802 adenocarcinomas (ADCA), 131 squamous carcinomas (SCC), and 3 carcinomas of non-specific histotype. Most institutions reported CPS and TPS data, whereas a minority used TAP. Overall, CPS, TPS, and TAP scores were in line with the data in literature and clinical trials for both ADCA and SCC, but inter-institutional heterogeneity was observed as represented by CPS ≥1 ADCA cases (range among institutions: 43.6%-100%). Inter-institutional heterogeneity was significantly associated with several variables, including (i) PD-L1 IHC case workload, with lower workload centers reporting more CPS ≥1 cases on average, and (ii) PD-L1 clone, with the 22C3 clone showing higher CPS scores than the SP263 clone. Tissue block aging was also significantly associated with a lower PD-L1 score, with a critical time window at 24-60 months.</div></div><div><h3>Conclusions</h3><div>This study confirms the alignment of GEC PD-L1 expression in Italian real-world practice with clinical trials. Inter-institutional variability and the significant influence of preanalytical factors, particularly tissue aging and PD-L1 clone, highlight important challenges in routine PD-L1 testing. Addressing these issues is crucial to enhance the reliability of PD-L1 IHC assessment and ensure optimal patient selection for ICIs in GEC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105846"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250485","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":"Survival outcomes and the role of DNADX ctDNA testing in patients treated with sacituzumab govitecan for metastatic breast cancer☆","authors":"S. Morganti ,&nbsp;R.J. Kusmick ,&nbsp;M.E. Hughes ,&nbsp;F. Brasó-Maristany ,&nbsp;K. Smith ,&nbsp;P. Tarantino ,&nbsp;R. Vega-Leon ,&nbsp;T. Grinda ,&nbsp;F. Pardo ,&nbsp;K. Dvir ,&nbsp;G.L. Suggs ,&nbsp;S. Buck ,&nbsp;M. Skeffington ,&nbsp;A.C. Garrido-Castro ,&nbsp;H.A. Parsons ,&nbsp;S.L. Sammons ,&nbsp;A. Prat ,&nbsp;N.U. Lin ,&nbsp;S.M. Tolaney ,&nbsp;A. Giordano","doi":"10.1016/j.esmoop.2025.105828","DOIUrl":"10.1016/j.esmoop.2025.105828","url":null,"abstract":"<div><h3>Background</h3><div>Sacituzumab govitecan (SG) is an anti-trop2 antibody–drug conjugate (ADC) approved for human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). However, data on effectiveness of SG and biomarkers remain limited. DNADX is a plasma-only multi-gene signature assay that identifies five tumor subtypes. In previous studies, DNADX subtypes have been associated with clinical outcomes.</div></div><div><h3>Materials and methods</h3><div>This study included patients with MBC treated with SG monotherapy between June 2014 and January 2023. Clinicopathological features and outcomes [time to next treatment (TTNT), overall survival (OS)] were analyzed. An exploratory analysis evaluated the association between DNADX subtypes and outcomes.</div></div><div><h3>Results</h3><div>A total of 121 patients with triple-negative breast cancer (TNBC), 59 with hormone receptor (HR)-positive/HER2-negative MBC, and 4 with HER2-positive MBC at the time of SG initiation were identified. Visceral disease was present in 75% of patients; 23.4% had brain metastases. Patients with TNBC had a median of 3 (range 0-9) prior lines for MBC, including chemotherapy (91%), immunotherapy (53%), and trastuzumab deruxtecan (T-DXd) (3%). Those with HR-positive/HER2-negative MBC had received a median of 5 (range 0-14) prior lines, including chemotherapy (97%), cyclin-dependent kinase 4/6 inhibitors (78%), immunotherapy (25%), and T-DXd (12%). Median TTNT was 4.3 months [95% confidence interval (CI) 3.7-5.0 months] for TNBC and 4.2 months (95% CI 2.8-4.9 months) for HR-positive/HER2-negative MBC. Median OS was 10.4 months (95% CI 8.0-13.3 months) for TNBC and 10.2 months (95% CI 7.0-12.6 months) for HR-positive/HER2-negative MBC. DNADX subtypes were significantly associated with outcomes. The tumor fraction (TF)-low subtype was linked to the longest TTNT and OS, while the proliferative and basal-related subtypes were associated with poorer outcomes.</div></div><div><h3>Conclusions</h3><div>Outcomes observed with SG were consistent with those reported in the registrational trials. DNADX subtypes were associated with TTNT and OS, underscoring their potential as biomarkers. Improved therapeutic options in the post-ADC setting and better biomarkers for treatment sequencing are urgently needed.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105828"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205967","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":"NALIRIFOX in the treatment of metastatic pancreatic ductal adenocarcinoma: an exploratory analysis of real-world data","authors":"A. Reichinger ,&nbsp;A. Friedrich ,&nbsp;T. Lentner ,&nbsp;H. Taghizadeh ,&nbsp;P. Reimann ,&nbsp;D. Nothdurfter ,&nbsp;J. Burghofer ,&nbsp;H. Windhager ,&nbsp;P. Kirchweger ,&nbsp;G. Webersinke ,&nbsp;T. Winder ,&nbsp;H. Rumpold ,&nbsp;B. Doleschal ,&nbsp;G.W. Prager","doi":"10.1016/j.esmoop.2025.105827","DOIUrl":"10.1016/j.esmoop.2025.105827","url":null,"abstract":"<div><h3>Background</h3><div>NALIRIFOX, a triplet chemotherapy regimen combining nanoliposomal irinotecan, 5-fluorouracil/leucovorin, and oxaliplatin, demonstrated superior survival outcomes versus gemcitabine plus nab-paclitaxel in the NAPOLI 3 trial for metastatic pancreatic ductal adenocarcinoma (mPDAC). However, its performance in routine clinical practice remains underexplored.</div></div><div><h3>Patients and methods</h3><div>This multicenter retrospective study evaluated the real-world efficacy and safety of NALIRIFOX as first-line treatment in 80 patients with mPDAC. Primary endpoints were time to failure of strategy (TFS) and overall survival (OS). Secondary endpoints included treatment-related toxicity, disease control rate (DCR), and molecular subgroup analyses based on homologous recombination repair mutations (HRRm) and <em>KRAS</em> status.</div></div><div><h3>Results</h3><div>Median TFS and OS were 5.66 and 11.15 months, respectively, with improved outcomes (TFS 6.05 months; OS 12.92 months) in patients meeting strict NAPOLI 3 inclusion criteria. DCR was 57.5%, and grade 3-4 toxicities occurred in 22.5% of patients—lower than reported in randomized trials. HRRm patients (20%) achieved significantly prolonged TFS (7.96 versus 5.23 months, <em>P</em> = 0.049) and OS (16.24 versus 11.11 months, <em>P</em> = 0.043). <em>KRAS</em> G12D/V mutations were associated with worse OS (11.15 months versus not reached, <em>P</em> &lt; 0.05), but not TFS.</div></div><div><h3>Conclusions</h3><div>This first real-world analysis of NALIRIFOX confirms its clinical effectiveness and manageable toxicity in an unselected patient population. The favorable outcomes in HRRm subgroups and the prognostic impact of <em>KRAS</em> variants underscore the need for molecular stratification in guiding first-line therapy for mPDAC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105827"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225330","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":"RSC4All as a machine learning nomogram to predict RSClin™ results in HR+/HER2- node-negative early breast cancer","authors":"F. Jacobs ,&nbsp;S. D’Amico ,&nbsp;E. Ferraro ,&nbsp;E. Agostinetto ,&nbsp;C. Tondini ,&nbsp;M. Gaudio ,&nbsp;C. Benvenuti ,&nbsp;R. Gerosa ,&nbsp;G. Saltalamacchia ,&nbsp;E. Zazzetti ,&nbsp;R. Di Rienzo ,&nbsp;R. Buonaiuto ,&nbsp;F. Martorana ,&nbsp;A. Chirco ,&nbsp;R. De Sanctis ,&nbsp;M.G. Della Porta ,&nbsp;A. Santoro ,&nbsp;P. Vigneri ,&nbsp;M.G. Arpino ,&nbsp;M. Giuliano ,&nbsp;A. Zambelli","doi":"10.1016/j.esmoop.2025.105830","DOIUrl":"10.1016/j.esmoop.2025.105830","url":null,"abstract":"<div><h3>Background</h3><div>RSClin™ combines clinicopathological (CP) and genomic data to refine predictions of distant recurrence (DR) risk and chemotherapy (CT) benefit in node-negative (N0) hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC). Available in the United States, RSClin™ is inaccessible in Europe due to regulatory constraints. We developed and validated RSC4All, a machine learning (ML) nomogram replicating RSClin™ predictions and evaluating clinical impact by comparing DR risk and CT benefit estimates across recurrence score (RS), RSClin™, and RSC4All.</div></div><div><h3>Materials and methods</h3><div>We retrospectively identified 290 HR-positive/HER2-negative eBC with both 21-gene RS and RSClin™ estimation at three European centers (development cohort). ML models were trained on 70% and internally validated on 30% of this cohort to reproduce RSClin™ estimates for DR risk and CT benefit. External validation used an independent cohort of 513 patients. Performance was assessed using receiver operating characteristic area under the curve (ROC AUC) (classification) and <em>R</em>^<em>2</em> (regression).</div><div>Clinical agreement between RSC4All and RSClin™ was evaluated using Cohen’s kappa and McNemar’s test, including replication of RS to RSClin™ reclassification patterns. RS and RSClin™ classifications were compared in the pooled population and CP predictors of reclassification were explored.</div></div><div><h3>Results</h3><div>ML classification models achieved excellent performance with ROC AUC 0.99 for both DR risk and CT benefit, while regression model had <em>R</em>^<em>2</em> = 0.82 and 0.77, respectively. In external validation, RSC4All maintained high accuracy (ROC AUC = 0.99; <em>R</em>^<em>2</em> = 0.82 and 0.76) with an almost perfect clinical agreement with RSClin™ (Cohen's kappa = 0.87 and 0.84) and replicated RS to RSClin™ reclassification direction in 94.1% (DR) and 93.0% (CT) of cases. In the pooled cohort, RSClin™ reclassified 22.2% of DR risk (balanced up/downgrades) and 12.2% for CT benefit (mostly upgrades), with high grade, high Ki-67, low progesterone receptor, and larger tumor size predicting upward reclassification. A web-based tool was developed for public access (<span><span>https://rsc4all.streamlit.app</span><svg><path></path></svg></span>).</div></div><div><h3>Conclusions</h3><div>RSC4All accurately reproduces RSClin™ predictions and reclassification patterns, providing a freely accessible alternative where RSClin™ is unavailable. By integrating CP and genomic data, it refines risk stratifications and supports adjuvant decisions in N0 HR-positive/HER2-negative eBC. External validation in an independent cohort strengthens its generalizability and clinical applicability.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105830"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250488","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":"Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with pancreatic cancer","authors":"D. Tai ,&nbsp;T. Conroy ,&nbsp;J.J.X. Lee ,&nbsp;C.E. Chee ,&nbsp;C.-Y. Hao ,&nbsp;I. Wijaya ,&nbsp;S. Aggarwal ,&nbsp;M. Ueno ,&nbsp;H.-C. Jeung ,&nbsp;N.M. Hashim ,&nbsp;J. Tan Chun Bing ,&nbsp;L.-T. Chen ,&nbsp;K. Korphaisarn ,&nbsp;S. Tanasanvimon ,&nbsp;W.-C. Chou ,&nbsp;E. Cargullo ,&nbsp;N.F.A. Muin ,&nbsp;M.A. Lee ,&nbsp;A. Ohba ,&nbsp;S. Bondarde ,&nbsp;M. Ducreux","doi":"10.1016/j.esmoop.2025.105826","DOIUrl":"10.1016/j.esmoop.2025.105826","url":null,"abstract":"<div><div>The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with pancreatic cancer, published in November 2023, were adapted in December 2024, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with pancreatic cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with pancreatic cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Singapore Society of Oncology (SSO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with pancreatic cancer across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials. Attention is drawn to the disparity in drug approvals and reimbursement strategies between the different countries.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105826"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257791","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":"Venous thromboembolic event risk with PARP inhibitors in solid tumors: a systematic review and meta-analysis","authors":"S.C. Yazgan ,&nbsp;E. Yekedüz ,&nbsp;E. Akkuş ,&nbsp;M. Sun ,&nbsp;S. Gillessen ,&nbsp;K. Fizazi ,&nbsp;R.R. McKay ,&nbsp;C. Ay ,&nbsp;E. Castro ,&nbsp;N. Agarwal ,&nbsp;T.K. Choueiri ,&nbsp;Y. Ürün","doi":"10.1016/j.esmoop.2025.105811","DOIUrl":"10.1016/j.esmoop.2025.105811","url":null,"abstract":"<div><h3>Background</h3><div>Poly (ADP-ribose) polymerase inhibitors (PARPi) are linked to thrombotic events, but the thrombosis risk in various cancers is unclear. This study evaluates the incidence and risk of venous thromboembolic events (VTEs) in patients with solid tumors treated with PARPi.</div></div><div><h3>Materials and methods</h3><div>This meta-analysis included randomized controlled phase II and III clinical trials in which patients with prostate, breast, ovarian, pancreatic, glioblastoma, small-cell lung (SCLC), and non-small-cell lung (NSCLC) cancers were treated with PARPi as monotherapy or in combination. The primary endpoint was to assess the frequency and risk of VTEs in patients treated with PARPi, while the secondary endpoint compared the incidence across different cancer subtypes.</div></div><div><h3>Results</h3><div>The analysis included 15 008 patients from 38 studies: 8805 in the PARPi group and 6203 in the control group. There were 11 ovarian cancer (<em>n</em> = 4348), 8 prostate cancer (<em>n</em> = 3872), 9 breast cancer (<em>n</em> = 4448), 4 NSCLC (<em>n</em> = 1063), and 3 SCLC (<em>n</em> = 583) studies, and 1 study each for pancreatic cancer (<em>n</em> = 50), glioblastoma (<em>n</em> = 123), and gastric (<em>n</em> = 521) cancer. The incidence of any-grade VTEs with PARPi was observed to be 2.4%, compared with 1.6% in controls, suggesting a possible increase in risk [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.00-1.88, <em>P</em> = 0.050]. This association appeared to be more pronounced in patients with prostate cancer (OR 1.98, 95% CI 1.06-3.70, <em>P</em> = 0.030) and pancreatic cancer (OR 7.22, 95% CI 1.40-37.25, <em>P</em> = 0.020).</div></div><div><h3>Conclusions</h3><div>While our findings indicate a possible association between PARPi and VTE risk in certain cancer types, this risk appears to be influenced by factors such as cancer subtype and treatment combinations. The overall contribution of PARPi monotherapy to VTE risk may be limited, and the results should be interpreted with caution due to study heterogeneity, wide CIs, and the absence of patient-level data.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105811"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198689","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":"Expression of antibody–drug conjugate targets in soft tissue sarcomas","authors":"F. Bertucci ,&nbsp;P. Finetti ,&nbsp;L. Mescam ,&nbsp;A. Monneur ,&nbsp;A. Frejafon ,&nbsp;A. Le Cesne ,&nbsp;I. Treilleux ,&nbsp;A. Italiano ,&nbsp;M. Brahmi ,&nbsp;J.-Y. Blay ,&nbsp;E. Mamessier","doi":"10.1016/j.esmoop.2025.105837","DOIUrl":"10.1016/j.esmoop.2025.105837","url":null,"abstract":"<div><h3>Background</h3><div>Soft tissue sarcomas (STSs) are aggressive and heterogeneous tumors with few efficient systemic therapies. Antibody–drug conjugates (ADCs) represent an emerging therapeutic option in oncology. Their efficacy is dependent on the expression of the ADC target on tumor cells. Very few data are available on ADC target expression in STSs.</div></div><div><h3>Materials and methods</h3><div>We analyzed the mRNA expression of 62 targets and 60 genes potentially involved in resistance/response to ADC in 1664 clinical primary tumors, including 476 liposarcomas (LPSs) 341 leiomyosarcomas, 330 undifferentiated pleomorphic sarcomas, 286 gastrointestinal stromal tumors, 126 synovial sarcomas, and 105 myxofibrosarcomas. Tumor expression in each type was compared with expression in 7414 normal tissue samples. To confirm the results at the protein level, we applied immunohistochemistry (IHC) to four ADC targets in another series of STS samples.</div></div><div><h3>Results</h3><div>Expression profiles of ADC targets were heterogeneous across and within all STS types. All types expressed multiple ADC targets. An overexpression rate of at least 25% of samples in at least one type was observed for 41 targets. The high target overexpression rate in some STS types suggested numerous new therapeutic opportunities not currently studied in clinical trials, such as PTK7 overexpressed in 81% of LPSs. In addition, co-expression of ADC-target pairs and of targets with signatures of vulnerability to immune checkpoint inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, and cyclin-dependent kinase (CDK)4/6 inhibitors was evidenced in the different pathological types, suggesting opportunities for testing ADC-based combinations. Finally, we showed heterogeneous expression profiles of potential ADC resistance/response genes between and within STS types. IHC confirmed the mRNA results for the four tested targets.</div></div><div><h3>Conclusion</h3><div>STSs express multiple target genes relevant for ADC treatment and expression varies between and within the pathological types. This comprehensive ADC target landscape, based on the largest molecular epidemiology study in STS, should help clinicians and drug developers for further evaluation of ADCs across STS types.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105837"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227276","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}