Journal of Clinical Oncology最新文献

{"title":"Letetresgene Autoleucel: A Milestone in Treatment of Myxoid/Round Cell Liposarcoma.","authors":"Emine Hatipoglu, Andrew J S Furness, Robin L Jones","doi":"10.1200/JCO-25-00055","DOIUrl":"10.1200/JCO-25-00055","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1755-1757"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complementing Anticancer Therapy: Antibody-Drug Conjugates Targeting CD46 as Prostate Cancer Treatment.","authors":"Natalia Kunz, Claudia Kemper","doi":"10.1200/JCO-25-00457","DOIUrl":"10.1200/JCO-25-00457","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1835-1838"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I, First-in-Human Study of FOR46 (FG-3246), an Immune-Modulating Antibody-Drug Conjugate Targeting CD46, in Patients With Metastatic Castration-Resistant Prostate Cancer.","authors":"Rahul R Aggarwal, Jacqueline Vuky, David VanderWeele, Matthew Rettig, Elisabeth I Heath, David Quigley, Jiaoti Huang, Arun Chumber, Alexander Cheung, Adam Foye, Stanley Leung, Jill Abbey, Andrew Dorr, Marc Nasoff, John Hunter, Steven Wang, Robert R Flavell, Lawrence Fong, Bin Liu, Eric J Small","doi":"10.1200/JCO-24-01989","DOIUrl":"10.1200/JCO-24-01989","url":null,"abstract":"<p><strong>Purpose: </strong>FOR46, a fully human antibody conjugated to monomethyl auristatin E, targets a tumor-selective epitope of CD46, which is overexpressed in metastatic castration-resistant prostate cancer (mCRPC). FOR46 demonstrates potent nonclinical activity in enzalutamide-resistant CRPC models.</p><p><strong>Patients and methods: </strong>This was a phase I, first-in-human, dose escalation/expansion study in patients with progressive mCRPC after treatment with ≥one androgen signaling inhibitors (ClinicalTrials.gov identifier: NCT03575819). The starting dose of FOR46 was 0.1 mg/kg given intravenously every 3 weeks. The primary objective was to determine the maximally tolerated dose (MTD). Whole-blood mass cytometry (cytometry by time of flight) was used to characterize peripheral immune response and CD46 expression in CRPC tissue that underwent central pathology review.</p><p><strong>Results: </strong>Fifty-six patients were enrolled. Dose-limiting toxicities included neutropenia (n = 4), febrile neutropenia (n = 1), and fatigue (n = 1). The MTD was 2.7 mg/kg using adjusted body weight. The most common grade ≥3 adverse events across all dose levels were neutropenia (59%), leukopenia (27%), lymphopenia (7%), anemia (7%), and fatigue (5%). One grade 3 febrile neutropenia event was observed. There were no treatment-related deaths. In the efficacy evaluable subset (patients with adenocarcinoma treated with a starting dose ≥1.2 mg/kg, n = 40), the median radiographic progression-free survival was 8.7 months (range, 0.1-33.9). Fourteen of 39 evaluable patients (36%) achieved a PSA50 response. The confirmed objective response rate was 20% (5 of 25 RECIST-evaluable patients). The median duration of response was 7.5 months. Responders had a significantly higher on-treatment frequency of circulating effector CD8⁺ T cells.</p><p><strong>Conclusion: </strong>FOR46 demonstrated encouraging preliminary clinical activity with a manageable safety profile. Targeting CD46 elicited an immune priming effect that was associated with clinical outcomes.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1824-1834"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tamales.","authors":"Megan M Dupuis","doi":"10.1200/JCO-25-00091","DOIUrl":"10.1200/JCO-25-00091","url":null,"abstract":"<p><p>@MissMeganEl shares a story reflecting on how patients invite us into their culture and their world and how this solidified her choice to be an oncologist.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1839-1840"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Models From Transcriptomic Signatures of the Tumor Microenvironment and Cell Cycle in Stage III Colon Cancer From PETACC-8 and IDEA-France Trials.","authors":"Claire Gallois, Marine Sroussi, Thierry André, Sophie Mouillet-Richard, Natacha Agueeff, Claire Mulot, Dewi Vernerey, Christophe Louvet, Jean-Baptiste Bachet, Louis-Marie Dourthe, Thibault Mazard, Marine Jary, Clélia Coutzac, Cédric Lecaille, Josep Tabernero, Jean-Luc Van Laethem, Côme Lepage, Jean-François Emile, Aurélien de Reyniès, Julien Taieb, Pierre Laurent-Puig","doi":"10.1200/JCO.23.02262","DOIUrl":"10.1200/JCO.23.02262","url":null,"abstract":"<p><strong>Purpose: </strong>The objective of this work was to establish prognostic models in stage III colon cancer (CC) on the basis of transcriptomic signatures of the tumor microenvironment (TME) and cell cycle from the PETACC-8 (training set) and IDEA-France (validation set) trials.</p><p><strong>Patients and methods: </strong>3'RNA sequencing was performed in 1,733 patients from the PETACC-8 trial and 1,248 patients from the IDEA-France trial. Four transcriptomic signatures were analyzed: T-cell and macrophage M2 signatures, the expression of CXCL13, and a score on the basis of the Oncotype DX CC Recurrence Score using the same formula from the stromal score and the cell cycle score. The Immune Proliferative Stromal (IPS) score was defined as the number of dichotomized signatures that fall under the category of a dismal prognosis (from 0 to 4). Time to recurrence (TTR) was defined as the time from the date of random assignment to local and/or metastatic relapse and/or death because of CC, whichever occurs first.</p><p><strong>Results: </strong>High Oncotype-like and M2 scores and low CXCL13 expression and T-cell score were associated with a shorter TTR. A multivariable model including these signatures and all known prognostic factors applied to the IDEA-France cohort by obtaining a value of this model for each patient showed TTR significantly different depending on the quartile of this value and a 3-year rate of patients without recurrence ranging from 56% for the lowest quartile to 89% for the highest quartile (<i>P</i> < .0001). The IPS score was significantly associated with TTR in multivariable analysis.</p><p><strong>Conclusion: </strong>Using transcriptomic data of patients with stage III CC from two large-scale adjuvant trials, a prognostic model on the basis of signatures of the TME and the cell cycle provides important information in addition to known prognostic factors for patient stratification on risk of recurrence.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1765-1776"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma.","authors":"Sandra P D'Angelo, Mihaela Druta, Brian A Van Tine, David Liebner, Scott M Schuetze, William D Tap, Jessica Preston, Sophia Goodison, Jimson W D'Souza, Gurpreet S Kapoor, Sunil Suchindran, Stefan Zajic, Aishwarya Bhaskar, Heather Kaczynski, Jaegil Kim, Erika Klohe, Ellie Corigliano, Ioanna Eleftheriadou, Michael J Nathenson, Neeta Somaiah","doi":"10.1200/JCO-24-01466","DOIUrl":"10.1200/JCO-24-01466","url":null,"abstract":"<p><strong>Purpose: </strong>The cancer/testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target in myxoid/round cell liposarcoma (MRCLS).</p><p><strong>Methods: </strong>In this pilot study, we assessed the adoptive T-cell therapy NY-ESO-1c²⁵⁹T letetresgene autoleucel (lete-cel) in patients with human leukocyte antigen (HLA)-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-positive advanced/metastatic NY-ESO-1-expressing MRCLS. Patients underwent a reduced-dose (cohort 1) or standard-dose (cohort 2) lymphodepletion regimen (LDR). The primary end point was investigator-assessed overall response rate (ORR). Safety was assessed through adverse event (AE) reports. Correlative biomarker analyses were performed post hoc. The trial is registered at ClinicalTrials.gov (identifier: NCT02992743).</p><p><strong>Results: </strong>Of 23 enrolled patients, 10 in cohort 1 and 10 in cohort 2 received lete-cel. Investigator-assessed ORR was 20% (95% CI, 2.5 to 55.6) and 40% (95% CI, 12.2 to 73.8), median duration of response was 5.3 months (95% CI, 1.9 to 8.7) and 7.5 months (95% CI, 6.0 to not estimable [NE]), and median progression-free survival was 5.4 months (95% CI, 2.0 to 11.5) and 8.7 months (95% CI, 0.9 to NE) in cohorts 1 and 2, respectively. AEs included cytokine release syndrome and cytopenias, consistent with T-cell therapy/LDR. Post hoc correlative biomarkers showed T-cell expansion and persistence in both cohorts.</p><p><strong>Conclusion: </strong>To our knowledge, this study is the first demonstrating the clinical promise of lete-cel in HLA-/NY-ESO-1-positive patients with advanced MRCLS.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1777-1788"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trend and Provider- and Organizational-Level Factors Associated With Early Palliative Care Billing Among Patients Diagnosed With Distant-Stage Cancers in 2010-2019 in the United States.","authors":"Xin Hu, Youngmin Kwon, Changchuan Jiang, Qinjin Fan, Kewei Sylvia Shi, Zhiyuan Jason Zheng, Jingxuan Zhao, Joan L Warren, K Robin Yabroff, Xuesong Han","doi":"10.1200/JCO-24-01935","DOIUrl":"10.1200/JCO-24-01935","url":null,"abstract":"<p><strong>Purpose: </strong>Early integration of specialized palliative care (PC) is recommended by clinical guidelines for advanced-stage cancers, but real-world evidence of its use is limited. We examined the recent trend of early PC billing among Medicare beneficiaries with distant-stage cancers and associated provider- and organization-level factors.</p><p><strong>Methods: </strong>Using SEER-Medicare data, we identified Medicare Fee-For-Service beneficiaries 65.5 years and older diagnosed with distant-stage female breast, colorectal, non-small cell lung, small cell lung, pancreatic, or prostate cancers in 2010-2019 with a survival of ≥6 months. Early PC billing was identified by diagnosis codes or hospice and palliative medicine (HPM) specialty codes on outpatient claims within first 3 months of cancer diagnosis or up to hospice admission date, whichever came first. Annual percentages of patients receiving early PC were assessed. We attributed treating physicians and organizations to patients and identified provider- and organization-level factors associated with early PC billing and the between-provider and between-organization variation in early PC billing using multivariable regressions.</p><p><strong>Results: </strong>Among 102,032 patients treated by 18,908 unique physicians, the percentage with early PC billing increased from 1.44% to 10.36% in 2010-2019 (<i>P</i> < .001). Treating physician's early PC referrals in the previous year and organizations' employment of any HPM specialist were associated with 3.01 percentage points (ppts, 95% CI, 2.50 to 3.52) and 4.54 ppts (95% CI, 3.65 to 5.42) higher likelihood of early PC billing. Between-provider variation in early PC was considerable but declined from 51.0% in 2010-2013 to 45.3% in 2017-2019. Similar patterns were found for between-organization variation.</p><p><strong>Conclusion: </strong>Despite growth in early PC billing among patients with distant-stage cancers in 2010-2019, its level remained low. Provider and organizational characteristics such as referral patterns and availability of HPM specialists within the organization may be important drivers for early PC utilization.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1789-1799"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized, Open-Label, Phase III Study of Tilsotolimod in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced Refractory Melanoma (ILLUMINATE-301).","authors":"Adi Diab, Paolo A Ascierto, Michele Maio, Reham Abdel-Wahab, Sylvie Negrier, Laurent Mortier, Petr Arenberger, Stephane Dalle, Ivana Krajsova, Luis de la Cruz, Marie-Therese Leccia, Michele Guida, Celeste Lebbe, Jean-Jacques Grob, Marcus O Butler, Gino K In, Carmen Loquai, John W T Walker, Victoria Atkinson, Ellen Kapiteijn, Sebastian Haferkamp, Srinivas Chunduru, Shahram Rahimian, Massimo Guidoboni, Caroline Robert","doi":"10.1200/JCO.24.00727","DOIUrl":"10.1200/JCO.24.00727","url":null,"abstract":"<p><strong>Purpose: </strong>There are limited treatment options for advanced melanoma that have progressed during or after immune checkpoint inhibitor therapy. Intratumoral (IT) immunotherapy may improve tumor-specific immune activation by promoting local tumor antigen presentation while avoiding systemic toxicities. The phase 3 ILLUMINATE-301 study (ClinicalTrials.gov identifier: NCT03445533) evaluated tilsotolimod, a Toll-like receptor-9 agonist, with or without ipilimumab in patients with anti-PD-1 advanced refractory melanoma.</p><p><strong>Methods: </strong>Patients with unresectable stage III-IV melanoma that progressed during or after anti-PD-1 therapy were randomly assigned 1:1 to receive 24 weeks of tilsotolimod plus ipilimumab or 10 weeks of ipilimumab alone. Nine IT injections of tilsotolimod were administered to a single designated lesion over 24 weeks. Intravenous ipilimumab 3 mg/kg was administered once every 3 weeks from week 2 in the tilsotolimod arm and week 1 in the ipilimumab arm. The primary end point was efficacy measured using objective response rate (ORR; independent review) and overall survival (OS).</p><p><strong>Results: </strong>A total of 481 patients received tilsotolimod plus ipilimumab (n = 238) or ipilimumab alone (n = 243). ORRs were 8.8% in the tilsotolimod arm and 8.6% in the ipilimumab arm, with disease control rates of 34.5% and 27.2%, respectively. Median OS was 11.6 months in the tilsotolimod arm and 10 months in the ipilimumab arm (hazard ratio, 0.96 [95% CI, 0.77 to 1.19]; <i>P</i> = .7). Grade ≥3 treatment-emergent adverse events occurred in 61.1% and 55.5% of patients in the tilsotolimod and ipilimumab arms, respectively.</p><p><strong>Conclusion: </strong>Combining IT tilsotolimod with ipilimumab did not significantly improve the ORR or OS compared with ipilimumab alone in patients with anti-PD-1 advanced refractory melanoma.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1800-1809"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Fertility Preservation in People With Cancer: ASCO Guideline Update.","authors":"H Irene Su, Christina Lacchetti, Joseph Letourneau, Ann H Partridge, Rubina Qamar, Gwendolyn P Quinn, Joyce Reinecke, James F Smith, Megan Tesch, W Hamish Wallace, Erica T Wang, Alison W Loren","doi":"10.1200/JCO-25-00662","DOIUrl":"10.1200/JCO-25-00662","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1847"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment Intensification Based on Residual Disease in Elderly Patients With AML.","authors":"Yutaka Shimazu, Yayoi Shimazu","doi":"10.1200/JCO-24-02645","DOIUrl":"10.1200/JCO-24-02645","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1841"},"PeriodicalIF":42.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}