ESMO Open最新文献

{"title":"HR-SC—an academic-developed machine learning framework to classify HRD-positive ovarian cancer patients and predict sensitivity to olaparib","authors":"L. Beltrame ,&nbsp;L. Mannarino ,&nbsp;A. Sergi ,&nbsp;A. Velle ,&nbsp;I. Treilleux ,&nbsp;S. Pignata ,&nbsp;L. Paracchini ,&nbsp;P. Harter ,&nbsp;G. Scambia ,&nbsp;F. Perrone ,&nbsp;A. González-Martin ,&nbsp;R. Berger ,&nbsp;L. Arenare ,&nbsp;S. Hietanen ,&nbsp;D. Califano ,&nbsp;S. Derio ,&nbsp;T. Van Gorp ,&nbsp;M.L. Dalessandro ,&nbsp;K. Fujiwara ,&nbsp;M. Provansal ,&nbsp;S. Marchini","doi":"10.1016/j.esmoop.2025.105060","DOIUrl":"10.1016/j.esmoop.2025.105060","url":null,"abstract":"<div><h3>Background</h3><div>High-grade serous ovarian cancer (OC) patients with defects in the homologous recombination repair (HRR) pathway benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. Clinically approved methods for identifying HRR status suffer from limitations, such as high failure rates and costs, leading to the clinical need for innovative approaches. To this aim, we developed Homologous Recombination Signature Classifier (HR-SC), a machine learning (ML) algorithm that integrates <em>BRCA1</em>/<em>BRCA2</em> status and copy number signatures, leveraging the availability of OC samples recruited from two international clinical trials, namely PAOLA-1 (dataset A) and MITO16A/MaNGO-OV2 (dataset B).</div></div><div><h3>Patients and methods</h3><div>569 DNA samples from datasets A and B were sequenced using a custom library design covering a backbone of structural regions and the full-length sequence of 375 genes. Data were used to train, validate (dataset A), and test (dataset B) HR-SC, using <em>BRCA1</em>/<em>BRCA2</em> status and a compendium of previously annotated copy number signatures. Lastly, HR-SC was compared with already established approaches to evaluate its predictive and prognostic role.</div></div><div><h3>Results</h3><div>In dataset A, where the failure rate was 6.4%, HR-SC showed a sensitivity of 92%, a specificity of 94.73%, an accuracy of 93.18%, a positive predictive value (PPV) of 95.83%, and a negative predictive value (NPV) of 90%. In dataset B, where the failure rate was 4%, HR-SC showed a sensitivity of 90.16%, a specificity of 82.86%, an accuracy of 87.5%, a PPV of 90.16%, and an NPV of 82.86%. Univariate and multivariate survival analyses demonstrated its predictive role [progression-free survival (PFS): hazard ratio (HR) = 0.42, <em>P</em> &lt; 0.0001; overall survival (OS): HR = 0.63, <em>P</em> = 0.036] and its prognostic role (PFS: HR = 0.56, <em>P</em> = 0.0095).</div></div><div><h3>Conclusions</h3><div>The study demonstrates that HR-SC is a novel, clinically feasible solution with a low failure rate for predicting HRR status in OC patients and underscores the importance of leveraging ML approaches for advancing precision oncology in the era of personalized medicine.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105060"},"PeriodicalIF":7.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089744","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":"Development and implementation of novel liquid biopsy NGS panels via the OncNGS precommercial procurement (PCP) initiative","authors":"G. Raicevic Toungouz ,&nbsp;R. Alessandrello ,&nbsp;P. Giacomini ,&nbsp;M. Kamal ,&nbsp;M. Gausachs ,&nbsp;L. Mazzarella ,&nbsp;P. Sujobert ,&nbsp;G. Frigè ,&nbsp;A. Alay ,&nbsp;J.M. Planchon ,&nbsp;O. Blau ,&nbsp;M.R. Mias Carballal ,&nbsp;H. Antoine-Poirel ,&nbsp;E. Nadal ,&nbsp;L. Bullinger ,&nbsp;A. Hebrant ,&nbsp;N. Servant ,&nbsp;N. D’Haene ,&nbsp;P. Aftimos ,&nbsp;E. Silkenstedt ,&nbsp;M. Van Den Bulcke","doi":"10.1016/j.esmoop.2025.105127","DOIUrl":"10.1016/j.esmoop.2025.105127","url":null,"abstract":"<div><h3>Background</h3><div>Circulating tumor DNA (ctDNA) analysis is transforming oncology, but challenges such as insufficient analytical sensitivity, difficult variant interpretation, suboptimal turnaround time, limited deployment flexibility, and high costs hinder its broader adoption and raise concerns about reimbursement sustainability across European health care systems.</div></div><div><h3>Materials and methods</h3><div>To address these challenges, we created the OncNGS consortium, comprising academic, public, and private hospitals (buyers’ group) and several supporting entities, to run a European precommercial procurement (PCP) initiative. The consortium defined ctDNA diagnostic testing requirements, conducted an open market consultation, and launched a call for tender. Suppliers were invited to develop an end-to-end, Conformité Européenne <em>In Vitro</em> Diagnostic (CE-IVD)-compliant solution integrating wet laboratory, dry laboratory, and reporting workflow in a single procedure, offering short turnaround time and reasonable cost.</div></div><div><h3>Results</h3><div>The OncNGS consortium defined criteria for a versatile, modular, cost-effective solution, deployable centrally or on-site, and adaptable to advancements in precision oncology. Launched in July 2022, the tender attracted seven companies, with four selected for phase I—OncNGS solution(s) design. From these, three advanced to phase II—prototyping. Ultimately, two contractors were awarded contracts for phase III to assess the clinical performance of their prototypes.</div></div><div><h3>Conclusions</h3><div>By leveraging the PCP approach, OncNGS aims to deliver innovative, affordable solutions to standardize ctDNA testing and reporting across European Union countries, improving diagnostic and therapeutic strategies for oncology patients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105127"},"PeriodicalIF":7.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089745","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":"First-in-human study of FAZ053, an anti-programmed death-ligand 1 (anti-PD-L1) monoclonal antibody, alone and in combination with spartalizumab, in patients with advanced malignancies","authors":"F. Janku ,&nbsp;D.S.P. Tan ,&nbsp;J. Martin-Liberal ,&nbsp;S. Takahashi ,&nbsp;R. Geva ,&nbsp;A. Gucalp ,&nbsp;A. Razak ,&nbsp;R. Kan ,&nbsp;R. Reiners ,&nbsp;J. Mataraza ,&nbsp;S. Szpakowski ,&nbsp;K. Subramanian ,&nbsp;X. Chen ,&nbsp;C. Lai ,&nbsp;P.L. Bedard","doi":"10.1016/j.esmoop.2025.105051","DOIUrl":"10.1016/j.esmoop.2025.105051","url":null,"abstract":"<div><h3>Background</h3><div>FAZ053 triggers an antitumor response by targeting programmed death-ligand 1 (PD-L1), thereby activating effector T cells and negatively regulating T cells. This study assessed the safety, tolerability, and preliminary efficacy of FAZ053 monotherapy and in combination with spartalizumab in patients with advanced solid tumors.</div></div><div><h3>Methods</h3><div>This phase I, multicenter, open-label study (NCT02936102) included dose escalation and dose expansion. The primary objectives were safety and tolerability; secondary objectives were pharmacokinetics, pharmacodynamics, and preliminary antitumor activity.</div></div><div><h3>Results</h3><div>Of the 154 patients treated, 49 (52.7%) patients receiving FAZ053 monotherapy experienced at least one treatment-related adverse event (TRAE), of whom 6 (6.5%) experienced grade ≥3 TRAEs; 35 patients (57.4%) receiving combination therapy experienced TRAEs, of whom 3 (4.9%) experienced grade ≥3 TRAEs. One patient who received FAZ053 1600 mg every 6 weeks (Q6W) and one who received FAZ053 20 mg every 3 weeks (Q3W) with spartalizumab 300 mg Q3W experienced dose-limiting toxicities of grade 4 creatinine increase and grade 3 liver function test increased, respectively. The median duration of exposure was 105 days for monotherapy and 85 days for combination therapy. During dose escalation, response was observed in 3 (5.1%) and 3 (4.9%) patients receiving FAZ053 monotherapy and combination therapy, respectively. In dose expansion, response was observed in 2 (50%) patients with advanced alveolar soft part sarcoma (ASPS) and 3 (30%) patients with advanced chordoma receiving FAZ053 monotherapy. FAZ053 demonstrated a dose-proportional pharmacokinetic profile with a terminal half-life of 20.6 days at 1200 mg Q3W. Biomarker analysis showed increased immune gene expression following FAZ053 treatment. The recommended dose for expansion was 1200 mg Q3W.</div></div><div><h3>Conclusion</h3><div>FAZ053 monotherapy was well tolerated and effective in maintaining disease control in various tumors including ASPS and chordoma. The anticipated synergistic effect of combined programmed cell death protein 1 (PD-1) and PD-L1 inhibition was not observed. These findings contribute to the growing evidence that rare, phenotypically ‘immune cold’ sarcomas, such as ASPS and chordoma, can become responsive to immune checkpoint inhibitors.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105051"},"PeriodicalIF":7.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070409","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 response re: factors associated with first-to-second line attrition among patients with metastatic breast cancer in the real-world","authors":"E. Blondeaux ,&nbsp;M. Lambertini ,&nbsp;F. Montemurro ,&nbsp;L. Del Mastro","doi":"10.1016/j.esmoop.2025.105107","DOIUrl":"10.1016/j.esmoop.2025.105107","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105107"},"PeriodicalIF":7.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070385","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":"Conditional progression-free survival in patients with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated with first-line ribociclib and endocrine therapy: real-world data from the RIBANNA study","authors":"T. Decker ,&nbsp;C. Brucker ,&nbsp;A. Engel ,&nbsp;P.A. Fasching ,&nbsp;T. Göhler ,&nbsp;C. Jackisch ,&nbsp;J. Janssen ,&nbsp;A. Köhler ,&nbsp;K. Lüdtke-Heckenkamp ,&nbsp;D. Lüftner ,&nbsp;F. Marmé ,&nbsp;M. van Mackelenbergh ,&nbsp;B. Rautenberg ,&nbsp;M. Schmidt ,&nbsp;R. Weide ,&nbsp;P. Wimberger ,&nbsp;E. Kisseleff ,&nbsp;C. Pfister ,&nbsp;C. Roos ,&nbsp;N. Wilhelm ,&nbsp;A. Wöckel","doi":"10.1016/j.esmoop.2025.105105","DOIUrl":"10.1016/j.esmoop.2025.105105","url":null,"abstract":"<div><h3>Background</h3><div>Progression-free survival (PFS) for patients with metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer significantly improved with cyclin-dependent kinase 4/6 inhibitors as part of first-line treatment. No data is available for these patients on how the risk of progression evolves. Therefore, we analyzed conditional PFS (cPFS), which reflects patient prognosis after initial management, that is, the probability of remaining free from progression in those who have already survived without progression for a given period.</div></div><div><h3>Patients and methods</h3><div>We analyzed PFS and cPFS for patients free from progression after 12, 24, and 36 months (reference time points) treated with ribociclib and endocrine therapy (ET) as first-line treatment for advanced HR+, HER2− breast cancer (aBC) within the RIBANNA noninterventional study (NCT06311383). Relevant subgroups with established prognostic factors were additionally examined.</div></div><div><h3>Results</h3><div>Compared with the median PFS of 35 months (95% confidence interval 32.3-38.4 months) in the overall population, the median cPFS was higher for all reference points: cPFS of 40.5 months (95% confidence interval 35.0-45.5 months) for patients who were progression-free 12 months, cPFS of 53.6 months (95% confidence interval 42.7-not reached months) for 24 months reference point, whereas for the 36 months reference point, the median cPFS was not reached. After patients had reached 2-year disease control, the initial presence of liver metastases or grade 3 disease no longer qualified as poor prognostic factors; internal organ metastases (central nervous system, liver, and lungs) showed a diminishing prognostic impact over time. A short treatment-free interval remained a relevant prognostic factor.</div></div><div><h3>Conclusion</h3><div>For the first time, increasing cPFS was demonstrated in patients treated with ribociclib and ET. Such information is highly relevant and reassuring for patients with HR+, HER2− aBC, and could be used to aid patient counseling and treatment decision-making, including possible de-escalation strategies. It is also a starting point for identifying dynamic prognostic factors related to long-term survival.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 6","pages":"Article 105105"},"PeriodicalIF":7.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070407","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":"66P Genetic insights into CDK4/6 inhibitor efficacy in invasive lobular carcinoma and invasive ductal carcinoma","authors":"E. Toda ,&nbsp;M. Hoshino ,&nbsp;T. Shimoi ,&nbsp;T. Yamanaka ,&nbsp;R. Kitadai ,&nbsp;A. Saito ,&nbsp;S. Kita ,&nbsp;A. Kawachi ,&nbsp;A. Maejima ,&nbsp;Y. Kojima ,&nbsp;E. Noguchi ,&nbsp;Y. Fujiwara ,&nbsp;K. Sudo ,&nbsp;T. Koyama ,&nbsp;K. Yonemori","doi":"10.1016/j.esmoop.2025.104620","DOIUrl":"10.1016/j.esmoop.2025.104620","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104620"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068093","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":"56P Neoadjuvant treatment with sequential letrozole and exemestane in postmenopausal patients with HR-positive, HER-2 negative breast cancer: Clinical and biomarker outcomes from the NEOLETEXE trial","authors":"K. Fjermeros ,&nbsp;J.J.G. Hettich ,&nbsp;S.B. Geisler ,&nbsp;B. Gravdehaug ,&nbsp;M. Seyedzadeh ,&nbsp;C.L. Hammarstrom ,&nbsp;E.B. Honigsperger ,&nbsp;S. Mathiassen ,&nbsp;T. Sauer ,&nbsp;J. Geisler","doi":"10.1016/j.esmoop.2025.104610","DOIUrl":"10.1016/j.esmoop.2025.104610","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104610"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068229","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":"4MO Development and validation of CDKPredX, a novel predictor of response to neoadjuvant endocrine therapy and CDK4/6 inhibitors versus chemotherapy in ER+/HER2- breast cancer: Correlative analysis of the randomized phase II PREDIX luminal B trial","authors":"T. Foukakis ,&nbsp;E. Tzoras ,&nbsp;M. Sarafidis ,&nbsp;E.G. Sifakis ,&nbsp;D. Salgkamis ,&nbsp;I. Zerdes ,&nbsp;K. Wang ,&nbsp;T. Pascual ,&nbsp;J. Gavilá-Gregori ,&nbsp;G. Villacampa ,&nbsp;A. Prat ,&nbsp;C.M. Perou ,&nbsp;J. Bergh ,&nbsp;T. Hatschek ,&nbsp;A. Matikas","doi":"10.1016/j.esmoop.2025.104559","DOIUrl":"10.1016/j.esmoop.2025.104559","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104559"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070653","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":"53P Tumor-agnostic detection and monitoring of circulating tumor DNA in HER2-positive early-stage breast cancer","authors":"M. Elliott ,&nbsp;Y. Gao ,&nbsp;J. Fuentes-Antras ,&nbsp;S. Main ,&nbsp;A. Dou ,&nbsp;E. Shah ,&nbsp;E. Amir ,&nbsp;M. Nadler ,&nbsp;C. Yu ,&nbsp;H. Berman ,&nbsp;L.L. Siu ,&nbsp;P.L. Bedard ,&nbsp;D. Cescon","doi":"10.1016/j.esmoop.2025.104607","DOIUrl":"10.1016/j.esmoop.2025.104607","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104607"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070658","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":"2O Integrating tumor infiltrating lymphocytes and nodal status for risk stratification in patients (pts) with triple-negative breast cancer (TNBC) and pathological complete response (pCR) after neoadjuvant treatment (NAT)","authors":"D. Massa ,&nbsp;S.O. Giacchetti ,&nbsp;C. Desmedt ,&nbsp;M. Kok ,&nbsp;P. Vigneri ,&nbsp;M. Ragazzi ,&nbsp;M. Lambertini ,&nbsp;C. Vernieri ,&nbsp;F. Piacentini ,&nbsp;C. Criscitiello ,&nbsp;L. Carbognin ,&nbsp;A. Botticelli ,&nbsp;L. Someil ,&nbsp;C. Bouchez ,&nbsp;G. Floris ,&nbsp;F. Martorana ,&nbsp;E. Lips ,&nbsp;S. Lando ,&nbsp;V. Guarneri ,&nbsp;M.V. Dieci","doi":"10.1016/j.esmoop.2025.104557","DOIUrl":"10.1016/j.esmoop.2025.104557","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104557"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068399","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}