Jama Oncology最新文献

{"title":"Tumor-Infiltrating Lymphocytes and Survival Outcomes in Early ERBB2-Positive Breast Cancer: 10-Year Analysis of the ShortHER Randomized Clinical Trial.","authors":"Maria Vittoria Dieci, Giancarlo Bisagni, Stefania Bartolini, Alessio Schirone, Luigi Cavanna, Antonino Musolino, Francesco Giotta, Anita Rimanti, Ornella Garrone, Elena Bertone, Katia Cagossi, Samanta Sarti, Antonella Ferro, Federico Piacentini, Enrico Orvieto, Melinda Sanders, Federica Miglietta, Davide Massa, Sara Balduzzi, Pierfranco Conte, Roberto D'Amico, Valentina Guarneri","doi":"10.1001/jamaoncol.2024.6872","DOIUrl":"10.1001/jamaoncol.2024.6872","url":null,"abstract":"<p><strong>Importance: </strong>For patients with early ERBB2 (formerly HER2)-positive breast cancer, there is a need to identify biomarkers to guide treatment de-escalation.</p><p><strong>Objective: </strong>To evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free (DDFS) and overall survival (OS) for patients with ERBB2-positive early breast cancer.</p><p><strong>Design, setting, and participants: </strong>The ShortHER randomized clinical trial was a multicentric trial in Italy that enrolled patients with ERBB2-positive breast cancer from December 2007 to October 2013. Patients received 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Tumor samples were evaluated for TILs. Herein, patients were evaluated at a median follow-up of 9 years, and data were analyzed from February 2023 to August 2024.</p><p><strong>Intervention: </strong>Four cycles of anthracycline-based chemotherapy followed by 4 courses of taxanes combined with trastuzumab for 1 year (long arm) or 3 courses of taxanes combined with trastuzumab for 9 weeks followed by reduced-dose anthracycline-based chemotherapy for 3 courses (short arm).</p><p><strong>Main outcomes and measures: </strong>The association of TILs with DDFS and OS was assessed with Cox models.</p><p><strong>Results: </strong>Of 1253 patients enrolled in the ShortHER trial, 866 women (median [IQR] age, 56 [48-64] years) had evaluable TILs. In Cox models with relevant factors, each 5% TIL increment was associated with improved DDFS (hazard ratio [HR], 0.87; 95% CI, 0.80-0.95; P = .001) and OS (HR, 0.89; 95% CI, 0.81-0.98; P = .01). The 10-year OS rate was 91.3% for patients with TILs 20% or higher, 93.3% for patients with TILs 30% or higher, and 98.1% for patients with TILs 50% or higher, resulting higher vs lower TIL counterparts. Patients with TILs lower than 20% showed a better outcome with the long vs short treatment (10-year DDFS, 88.7% vs 81.0%), whereas patients with TILs 20% or higher showed the opposite (10-year DDFS, 87.1% vs 92.2%; P for interaction = .01). Similarly, patients with TILs 20% or higher had a 10-year OS rate of 89.3% in the long arm vs 93.1% in the short arm (HR, 0.36; 95% CI, 0.10-1.36); patients with TILs lower than 20% had a 10-year OS rate of 91.3% in the long arm vs 86.9% in the short arm (HR, 1.36; 95% CI, 0.82-2.23; P for interaction = .06).</p><p><strong>Conclusions and relevance: </strong>This follow-up analysis of the ShortHER randomized clinical trial is, to our knowledge, the first demonstration of an independent effect of TILs in terms of OS for patients with ERBB2-positive early breast cancer treated with adjuvant chemotherapy and anti-ERBB2 therapy. Patients with TILs 20% or higher who de-escalated trastuzumab duration and chemotherapy dose were not exposed to an excess risk of distant relapse or death.</p><p><strong>Trial registration: </strong>EudraCT: 2007-004326-25.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"386-393"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411292","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":"Endocrine Therapy Interruption, Resumption, and Outcomes Associated With Pregnancy After Breast Cancer.","authors":"Julia D Ransohoff, Rebecca M Lewinsohn, James Dickerson, Ingrid Luo, Mina Satoyoshi, Victor Ritter, Rachael Chavez, Amanda J Wheeler, Su-Ying Liang, Pragati Kenkare, Scarlett L Gomez, Lidia Schapira, Esther M John, Summer S Han, Allison W Kurian","doi":"10.1001/jamaoncol.2024.6868","DOIUrl":"10.1001/jamaoncol.2024.6868","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"423-426"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411290","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":"A Call for Improved Guidance to Integrate Modern Biomarkers Into Routine Clinical Care-Piecing the Puzzle Together.","authors":"Catherine Dunn, Jeanne Tie, Peter Gibbs","doi":"10.1001/jamaoncol.2024.6479","DOIUrl":"10.1001/jamaoncol.2024.6479","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"367-368"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257038","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":"Novel Combination Immunotherapy and Clinical Activity in Patients With HPV-Associated Cancers: A Nonrandomized Clinical Trial.","authors":"Charalampos S Floudas, Meghali Goswami, Renee N Donahue, Danielle M Pastor, Jason M Redman, Isaac Brownell, Evrim B Turkbey, Lisa M Cordes, Seth M Steinberg, Michell Manu, Deneise C Francis, Elizabeth Lamping, Jennifer L Marté, Mary Kackley, Elizabeth Krauss, Manuk Manukyan, Caroline Jochems, Jeffrey Schlom, James L Gulley, Julius Strauss","doi":"10.1001/jamaoncol.2024.6998","DOIUrl":"10.1001/jamaoncol.2024.6998","url":null,"abstract":"<p><strong>Importance: </strong>Patients who experience progression of advanced human papillomavirus (HPV)-associated cancers and who have previously received first-line systemic treatment have a poor prognosis and limited therapeutic options.</p><p><strong>Objective: </strong>To assess the clinical activity of the combination of the HPV type 16 therapeutic vaccine PDS0101, the tumor-targeting interleukin 12 antibody-drug conjugate PDS01ADC, and the bifunctional anti-programmed cell death ligand 1 (PD-L1)/transforming growth factor β (TGF-β) bintrafusp alfa in advanced HPV-associated cancers.</p><p><strong>Design, setting, and participants: </strong>This nonrandomized clinical trial was phase 1/2 and investigator initiated, and was conducted at a single US cancer research center between June 2020 and July 2022. Patients with advanced or metastatic HPV-associated cancers were eligible, including patients who were both immune checkpoint blockade (ICB) naive and ICB resistant. The cutoff date for data analysis was May 13, 2024.</p><p><strong>Intervention: </strong>Patients received 1 mL of PDS0101 subcutaneously every 4 weeks for 6 doses then every 12 weeks for 2 additional doses, PDS01ADC, 16.8 µg/kg, subcutaneously every 4 weeks or PDS01ADC, 8 µg/kg, subcutaneously every 2 weeks, and bintrafusp alfa, 1200 mg, intravenously every 2 weeks.</p><p><strong>Main outcomes and measures: </strong>Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.1 in ICB-naive patients.</p><p><strong>Results: </strong>Of the 50 eligible patients, 26 (52%) were men and the median age was 56 years (range, 28-80 years). The median (IQR) follow-up was 37.7 (30.6-42.0) months. Fourteen patients (28%) were ICB naive, with an ORR of 35.7% (95% CI, 12.8%-64.9%), and median overall survival (OS) 42.4 months (95% CI, 8.3 months-not estimable); in ICB-resistant patients, the ORR was 16.7% (6 of 36 patients; 95% CI, 6.4%-32.8%) and median OS was 15.8 months (95% CI, 9.0-21.3 months). Among patients with HPV-16-positive tumors (37 patients [74%]), in the ICB-naive group (8 patients [21.6%]) the ORR was 62.5% (95% CI, 24.5%-91.5%) and a median OS measure was not reached. Grade 3 and 4 treatment-related adverse events occurred in 26 of 50 patients (52%). There were no treatment-related deaths.</p><p><strong>Conclusions and relevance: </strong>In this trial, the combination of PDS0101, PDS01ADC, and bintrafusp alfa showed an acceptable safety profile and promising antitumor activity and improved OS in patients with HPV-16-positive cancers, in both ICB-naive and ICB-resistant patients, warranting further evaluation of the combination of PDS0101 and PDS01ADC with simultaneous PD-L1/TGF-β inhibition in these populations.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04287868.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"394-399"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460271","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":"JAMA Oncology.","authors":"","doi":"10.1001/jamaoncol.2024.4637","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4637","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":"11 4","pages":"365"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038673","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":"Improving the Clinical Utility of FRAX in Patients With Cancer-The Need for More Detailed Analysis.","authors":"Chien-Min Lien, Ming-Jen Wang, Ching-Mao Chang","doi":"10.1001/jamaoncol.2024.7009","DOIUrl":"10.1001/jamaoncol.2024.7009","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"433-434"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460316","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":"Efficacy of Hand Cooling and Compression in Preventing Taxane-Induced Neuropathy: The POLAR Randomized Clinical Trial.","authors":"Laura L Michel, Daniel Schwarz, Philipp Romar, Manuel Feisst, Daniel Hamberger, Anastasia Priester, Eileen Kurre, Eva Klein, Jana Müller, Timo Schinköthe, Markus Weiler, Katharina Smetanay, Carlo Fremd, Sabine Heublein, Verena Thewes, Michael O Breckwoldt, Dirk Jäger, Martin Bendszus, Frederik Marmé, Andreas Schneeweiss","doi":"10.1001/jamaoncol.2025.0001","DOIUrl":"10.1001/jamaoncol.2025.0001","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting adverse effect of taxane-based chemotherapies. Currently, there is no established strategy for prevention or treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To compare the effectiveness of 1-sided hand cooling and compression for preventing CIPN in patients with primary breast cancer receiving taxane-based chemotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;The POLAR randomized clinical trial was conducted at the National Center for Tumor Diseases Heidelberg between November 2019 and January 2022. Female patients with breast cancer who received weekly nab-paclitaxel-based or paclitaxel-based neoadjuvant or adjuvant chemotherapy were enrolled. Patients with prior chemotherapy, preexisting neuropathy, or neuropathy-related comorbidities were excluded.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;Patients were randomized 1:1 to cooling or compression of the dominant hand. No intervention was performed on the other hand. Cooling was performed with a frozen glove and compression was applied by 2 surgical gloves (1 size smaller than the tight-fitting size) 30 minutes before, after, and during taxane administration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;The primary end point was the efficacy to prevent grade 2 or higher sensory CIPN evaluated by Common Terminology Criteria for Adverse Events, version 5.0. Further CIPN assessment included the clinical version of the Total Neuropathy Score and QLQ CIPN20. CIPN rates were compared between intervention groups. Nail toxic effects, quality of life, CIPN-associated dose reductions, treatment discontinuations, and risk factors were evaluated. Follow-up examinations were performed 1 week, 1 month, and 6 to 8 months after the last taxane dose.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 122 female patients with primary breast cancer (mean [SD] age, 50 [12] years) were randomized to either cooling or compression of the dominant hand. Twenty-one individuals withdrew from the study, so 101 patients were included in the final analysis (n = 52 and n = 49 for cooling and compression, respectively). Both interventions significantly reduced the incidence of grade 2 or higher CIPN (cooling: 15 participants experiencing high-grade CIPN in the cooling arm [29%] vs 26 in the control arm [50%]; P = .002; effect size, 21.15% [95% CI, 5.98%-35.55%]; compression: 12 participants experiencing CIPN in the intervention arm [24%] vs 19 in the control arm [38%]; P = .008; effect size, 14.29% [95% CI, 2.02%-27.24%]). CIPN was the main reason for treatment discontinuations in 16 of 24 participants (67%). The predominant risk factors were the cumulative taxane dosage and the neurotoxic agent. Participants experiencing grade 2 or higher CIPN showed a reduced global health status during and 6 to 8 months after taxane therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;In this randomized clinical trial, ","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"408-415"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568522","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":"Improving the Clinical Utility of FRAX in Patients With Cancer-The Need for More Detailed Analysis-Reply.","authors":"Carrie Ye, William D Leslie, Harminder Singh","doi":"10.1001/jamaoncol.2024.7012","DOIUrl":"10.1001/jamaoncol.2024.7012","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"434-435"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460254","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":"Against All Odds.","authors":"Ankit S Shah","doi":"10.1001/jamaoncol.2024.6724","DOIUrl":"10.1001/jamaoncol.2024.6724","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"373-374"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411288","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":"Can Knowledge From Treating Chronic Myeloid Leukemia Inform Therapy of EGFR-Mutant Lung Adenocarcinoma?","authors":"Robert Peter Gale","doi":"10.1001/jamaoncol.2024.6727","DOIUrl":"10.1001/jamaoncol.2024.6727","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"369-370"},"PeriodicalIF":28.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460288","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}