ESMO Open最新文献

{"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}

{"title":"81P Tumor-infiltrating lymphocyte clustering and survival associations in luminal breast cancer from: TCGA and SCAN-B","authors":"F.J. Fernández Hernández ,&nbsp;S.P. Gampenrieder ,&nbsp;G. Rinnerthaler ,&nbsp;M. Balic ,&nbsp;S. Vosberg","doi":"10.1016/j.esmoop.2025.104635","DOIUrl":"10.1016/j.esmoop.2025.104635","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104635"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068587","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":"78P Validation of an AI-based solution for breast cancer risk stratification using digital H&E images: Subgroup analysis within PANTHER clinical trial","authors":"E. Tzoras ,&nbsp;D. Salgkamis ,&nbsp;N. Tsiknakis ,&nbsp;H. Johansson ,&nbsp;W. Sun ,&nbsp;M. Hellström ,&nbsp;A. Andersson ,&nbsp;S. Loibl ,&nbsp;M. Untch ,&nbsp;C. Denkert ,&nbsp;P. Jank ,&nbsp;M. Rantalainen ,&nbsp;J. Hartman ,&nbsp;I. Zerdes ,&nbsp;A. Matikas ,&nbsp;J. Bergh ,&nbsp;T. Foukakis","doi":"10.1016/j.esmoop.2025.104632","DOIUrl":"10.1016/j.esmoop.2025.104632","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 104632"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070197","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}