Jama Oncology最新文献_第5页

Transarterial Chemoembolization Plus Thermal Ablation in Unresectable Hepatocellular Carcinoma: The Phase 3 TORCH Randomized Clinical Trial. 经动脉化疗栓塞加热消融治疗不可切除的肝细胞癌：3期TORCH随机临床试验

IF 20.1 1区医学

Jama Oncology Pub Date : 2026-09-01 DOI: 10.1001/jamaoncol.2026.2366

Ning Lyu, Jun-Zhe Yi, Xin-Tong Wu, Yi-Min Zhang, Tao Pan, Lu-Wen Mu, Song Chen, Jiong-Liang Wang, Jie Xu, Gen-Jun Tan, Yu-Nan Zhang, Zu-Qing Gao, Zi-Xi Ou-Yang, Wei-Jie Wu, Yu-Jia Song, Hai-Jing Deng, Meng He, Yi-Quan Jiang, Qi-Feng Chen, Ji-Bin Li, Ming Shi, Min-Shan Chen, Ming Zhao

{"title":"Transarterial Chemoembolization Plus Thermal Ablation in Unresectable Hepatocellular Carcinoma: The Phase 3 TORCH Randomized Clinical Trial.","authors":"Ning Lyu, Jun-Zhe Yi, Xin-Tong Wu, Yi-Min Zhang, Tao Pan, Lu-Wen Mu, Song Chen, Jiong-Liang Wang, Jie Xu, Gen-Jun Tan, Yu-Nan Zhang, Zu-Qing Gao, Zi-Xi Ou-Yang, Wei-Jie Wu, Yu-Jia Song, Hai-Jing Deng, Meng He, Yi-Quan Jiang, Qi-Feng Chen, Ji-Bin Li, Ming Shi, Min-Shan Chen, Ming Zhao","doi":"10.1001/jamaoncol.2026.2366","DOIUrl":"10.1001/jamaoncol.2026.2366","url":null,"abstract":"Importance: Transarterial chemoembolization (TACE) is the standard of care for liver-confined hepatocellular carcinoma (HCC) that is not amenable to curative treatment; however, TACE has demonstrated unsatisfactory survival benefits.Objective: To evaluate whether combining TACE with subsequent thermal ablation improves clinical outcomes compared with TACE alone in patients with liver-confined unresectable HCC.Design, setting, and participants: The open-label, phase 3 TORCH randomized clinical trial was conducted from May 2015 to August 2024 at 2 tertiary medical centers in China. Patients with Barcelona Clinic Liver Cancer stage B HCC were enrolled. The data cutoff was October 31, 2025.Interventions: Patients were randomly assigned (1:1) to receive either TACE combined with subsequent selective radiofrequency ablation (TACE-ablation) or TACE alone.Main outcomes and measures: The primary end point was progression-free survival (PFS), assessed per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Secondary end points included overall survival (OS), treatment response and PFS per modified RECIST, untreatable PFS, and safety.Results: Among 241 patients included in the intention-to-treat population, 121 received TACE-ablation (median [IQR] age, 59.0 [51.0-66.0] years; 108 [89.3%] male), and 120 received TACE alone (mean [IQR] age, 58.0 [50.0-64.0]; 106 [88.3] male). The number of patients with 6-and-12 tumor burden scores of lower than 6, 6 to 12, and more than 12 points were 34 (28.1%), 79 (65.3%), and 8 (6.6%) in the TACE-ablation group and 31 (25.8%), 76 (63.3%), and 13 (10.8%) in the TACE alone group, respectively. At the data cutoff, the median PFS per RECIST, version 1.1, was 17.7 months (95% CI, 11.4-23.1 months) in the TACE-ablation group vs 7.3 months (95% CI, 6.4-10.4 months) in the TACE alone group (hazard ratio [HR], 0.47; 95% CI, 0.34-0.65; P < .001). TACE-ablation also resulted in statistically significant prolonged untreatable PFS compared with TACE (35.1 months vs 12.3 months; HR, 0.40; 95% CI, 0.27-0.58; P < .001). Median OS was 88.6 months (95% CI, 43.1 months to not estimable) with TACE-ablation and 35.1 months (95% CI, 25.4-45.5 months) with TACE alone (HR, 0.50; 95% CI, 0.34-0.73; P < .001). Clinically meaningful improvements in both PFS and OS were observed in patients with low to moderate tumor burden scores (≤6 and 6-12 points). Grade 3 and 4 treatment-related adverse events occurred in 23 patients (23.2%) in the TACE-ablation group and 24 (18.3%) in the TACE alone group.Conclusions and relevance: In this phase 3 randomized clinical trial, TACE combined with subsequent thermal ablation demonstrated superior survival outcomes than TACE alone in patients with liver-confined unresectable HCC. Sequential TACE-ablation could serve as a feasible treatment","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"980-989"},"PeriodicalIF":20.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622164","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}

引用次数: 0

Cemiplimab and Fianlimab With Neoadjuvant Chemotherapy in Early-Stage High-Risk ERBB2-Negative Breast Cancer: The I-SPY2 Randomized Clinical Trial. 早期高危erbb2阴性乳腺癌的新辅助化疗：I-SPY2随机临床试验

IF 20.1 1区医学

Jama Oncology Pub Date : 2026-09-01 DOI: 10.1001/jamaoncol.2026.2576

Claudine Isaacs, Rita Nanda, Christina Yau, A Jo Chien, Dawn L Hershman, Erica M Stringer-Reasor, Anne M Wallace, Alexandra Thomas, Christos Vaklavas, Amy S Clark, Laura C Kennedy, Amy Sanford, Judy C Boughey, Kathy S Albain, Lajos Pusztai, Kevin M Kalinsky, Heather Beckwith, Nicole O Williams, Hyo S Han, Carla Falkson, Mili Arora, Anthony D Elias, Paula R Pohlmann, Mariya Rozenblit, Natalie Marshall, Yunn-Yi Chen, Meghna S Trivedi, Julia E McGuinness, Frederick M Howard, Nan Chen, Katia Khoury, Rachael B Lancaster, Kay T Yeung, Emily Douglas, Mei Wei, Candace Mainor, Barbara LeStage, Amy L Delson, Adam L Asare, Lamorna Brown-Swigart, Gillian L Hirst, Jeffrey B Matthews, Jane Perlmutter, W Fraser Symmans, Douglas Yee, Nola M Hylton, Laura J van 't Veer, Hope S Rugo, Angela M DeMichele, Donald A Berry, Laura J Esserman

{"title":"Cemiplimab and Fianlimab With Neoadjuvant Chemotherapy in Early-Stage High-Risk ERBB2-Negative Breast Cancer: The I-SPY2 Randomized Clinical Trial.","authors":"Claudine Isaacs, Rita Nanda, Christina Yau, A Jo Chien, Dawn L Hershman, Erica M Stringer-Reasor, Anne M Wallace, Alexandra Thomas, Christos Vaklavas, Amy S Clark, Laura C Kennedy, Amy Sanford, Judy C Boughey, Kathy S Albain, Lajos Pusztai, Kevin M Kalinsky, Heather Beckwith, Nicole O Williams, Hyo S Han, Carla Falkson, Mili Arora, Anthony D Elias, Paula R Pohlmann, Mariya Rozenblit, Natalie Marshall, Yunn-Yi Chen, Meghna S Trivedi, Julia E McGuinness, Frederick M Howard, Nan Chen, Katia Khoury, Rachael B Lancaster, Kay T Yeung, Emily Douglas, Mei Wei, Candace Mainor, Barbara LeStage, Amy L Delson, Adam L Asare, Lamorna Brown-Swigart, Gillian L Hirst, Jeffrey B Matthews, Jane Perlmutter, W Fraser Symmans, Douglas Yee, Nola M Hylton, Laura J van 't Veer, Hope S Rugo, Angela M DeMichele, Donald A Berry, Laura J Esserman","doi":"10.1001/jamaoncol.2026.2576","DOIUrl":"10.1001/jamaoncol.2026.2576","url":null,"abstract":"Importance: Although adding immune checkpoint inhibitors to neoadjuvant chemotherapy improves outcomes in high-risk early-stage breast cancer, opportunities remain to further enhance response. Dual checkpoint blockade offers a potential strategy to further enhance efficacy.Objective: To evaluate the combination of anti-programmed cell death 1 protein (PD-1) cemiplimab and anti-lymphocyte activation gene 3 (LAG-3) added to neoadjuvant therapy in ERBB2-negative early-stage, high-risk breast cancer.Design, setting, and participants: The I-SPY2 (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2) is an ongoing randomized clinical platform trial being conducted at multiple US clinical sites including patients with early-stage (II or III) ERBB2-negative, high-risk breast cancer. Participants, continuously enrolled since 2010, were adaptively randomized from February 2, 2020, to December 9, 2021, to one of several experimental neoadjuvant therapies or control groups based on receptor subtypes defined by hormone receptor (HR), ERBB2 status, and MammaPrint (Agendia Inc) molecular risk, categorized as high (MP1) or ultrahigh (MP2). Data were analyzed from January 1, 2022, to August 5, 2025.Interventions: Both groups received weekly paclitaxel for 12 weeks, then doxorubicin and cyclophosphamide followed by surgery; concomitant with paclitaxel, the intervention group also received 4 doses of cemiplimab and fianlimab (PCF) every 3 weeks.Main outcomes and measures: Pathologic complete response (pCR). Treatments graduated when they achieved 85% bayesian probability of success in a subtype-specific phase 3 trial. Pathway-specific biomarkers were assessed for response prediction.Results: A total of 78 participants (mean [SD] age, 47 [39-54] years) were randomized to the intervention group, with 350 participants (mean [SD] age, 48 [39-57] years) randomized to the historical control population. PCF graduated in all clinical signatures, with pCR rates vs control of 44% (95% CI, 34%-53%) vs 21% (95% CI, 17%-25%) in all ERBB2, 53% (95% CI, 39%-67%) vs 29% (95% CI, 22%-36%) in triple-negative, and 36% (95% CI, 23%-49%) vs 14% (95% CI, 9%-19%) in HR-positive and ERBB2-negative disease. Among the total participants, 16 (21%) experienced adrenal insufficiency, including hypophysitis (11% grade 3 or 4), mostly occurring after immunotherapy completion. PCF was found to be highly effective in the subset of patients with immune signature positive status (ImPrint positive).Conclusions and relevance: In this randomized clinical trial, the combination of PD-1 and anti-LAG-3 inhibition with standard NAC was effective in early-stage ERBB2-negative breast cancer, particularly in patients displaying a positive ImPrint immune signature. These results warrant further d","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"1008-1017"},"PeriodicalIF":20.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622212","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}

引用次数: 0

Considerations in Genomic Therapy Matching. 基因组治疗匹配的考虑。

IF 20.1 1区医学

Jama Oncology Pub Date : 2026-09-01 DOI: 10.1001/jamaoncol.2026.2248

Polina Shilo