JAMA Oncology最新文献

{"title":"Benmelstobart With or Without Anlotinib After Chemoradiotherapy for Unresectable Non−Small Cell Lung Cancer","authors":"Yongling Ji, Qiwen Li, Long Chen, Qingsong Pang, Ou Jiang, Yuanyuan Chen, Jin Wang, Hong Ge, Yufeng Cheng, Rongrong Zhou, Xiangjiao Meng, Xuhong Min, Hui Wang, Haihua Yang, Yue Xie, Anping Zheng, Jie Li, Bing Xia, Desheng Hu, Xi Zhang, Fang Peng, Wenhui Li, Baoqing Chen, Rui Li, Shuohan Zheng, Ling Cai, Shubi Li, Yujin Xu, Wei Feng, Xiaojing Lai, Liming Sheng, Xiaojiang Sun, Zhun Wang, Min Fang, Yang Yang, Yin Yang, Ming Chen","doi":"10.1001/jamaoncol.2026.3918","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.3918","url":null,"abstract":"Importance Consolidation immunotherapy improves outcomes after chemoradiotherapy for unresectable stage III non–small cell lung cancer (NSCLC). Disease progression remains common, and more effective consolidation strategies are needed. Objective To evaluate the efficacy and safety of benmelstobart with or without anlotinib as consolidation therapy after chemoradiotherapy for unresectable stage III NSCLC. Design, Setting, and Participants This multicenter double-blind phase 3 randomized clinical trial took place at 42 centers in China from 2020 to 2023 among patients with unresectable stage III NSCLC without progression after concurrent or sequential chemoradiotherapy. In stage 1, patients were randomized 1:1:1 to 2 active regimens or placebo; in stage 2, additional patients were randomized 1:1 between the active regimens to power their direct comparison. Data cutoffs were November 30, 2023, for stage 1 and July 8, 2024, for the pooled analysis. Data analysis was performed from January 17 to March 23, 2025. Interventions Patients were randomized to receive benmelstobart plus anlotinib, benmelstobart plus anlotinib placebo, or their matching placebos. Main Outcomes and Measures Primary end point was independent review committee (IRC)−assessed progression-free survival (PFS). Results Of 553 participants (median [IQR] age, 62 [56-67] years; 495 male individuals [89.5%]), 390 were randomized in stage 1 and 163 in stage 2. In stage 1, median PFS was 15.1 months (95% CI, 9.4-21.7) with benmelstobart plus anlotinib, 9.7 months (95% CI, 6.0-34.4) with benmelstobart alone, and 4.2 months (95% CI, 3.2-6.8) with placebo. The hazard ratios (HRs) were 0.49 (95% CI, 0.36-0.66; <jats:italic>P</jats:italic> &amp;amp;lt; .001) for benmelstobart plus anlotinib vs placebo and 0.53 (95% CI, 0.39-0.72; <jats:italic>P</jats:italic> &amp;amp;lt; .001) for benmelstobart vs placebo. In the pooled stage 1 and 2 analysis, median PFS was 17.4 (95% CI, 12.5-24.8) months with benmelstobart plus anlotinib and 11.2 (95% CI, 7.0-20.7) months with benmelstobart alone (HR, 0.82; 95% CI, 0.63-1.08; <jats:italic>P</jats:italic> = .12). Grade 3 to 5 treatment-related adverse events occurred in 48.8%, 29.4%, and 19.7% in the benmelstobart plus anlotinib, benmelstobart alone, and placebo groups, respectively; grade 5 events occurred in 7.2%, 1.4%, and 1.5%, respectively. Conclusions and Relevance This randomized clinical trial found that benmelstobart with or without anlotinib significantly improved PFS compared with placebo. Adding anlotinib did not significantly improve PFS compared with benmelstobart alone and increased severe and fatal treatment-related adverse events. Trial Registration ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT04325763\">NCT04325763</jats:ext-link>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"37 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293043","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":"FGFR Alterations in Bladder Cancer—From Molecular Pathogenesis to Precision Oncology","authors":"Katrina Collins, Liang Cheng","doi":"10.1001/jamaoncol.2026.4196","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.4196","url":null,"abstract":"Importance Alterations in the fibroblast growth factor receptor (FGFR) pathway, particularly <jats:italic toggle=\"yes\">FGFR3</jats:italic> , are among the most common genomic events in urothelial carcinoma (UC) and represent a cornerstone of precision oncology. Although <jats:italic toggle=\"yes\">FGFR3</jats:italic> alterations predominate, selected <jats:italic toggle=\"yes\">FGFR2</jats:italic> fusions also identify patients who may benefit from targeted therapy. This review summarizes the biology, molecular diagnostics, and evolving clinical applications of FGFR alterations in UC. Observations <jats:italic toggle=\"yes\">FGFR2/3</jats:italic> alterations are clinically actionable biomarkers across non–muscle-invasive, muscle-invasive, metastatic, and upper-tract UC. Comprehensive genomic profiling, tissue sequencing, plasma circulating tumor DNA, urine-based molecular assays, and molecular residual disease assessment are expanding their roles in diagnosis, treatment selection, surveillance, and disease monitoring. Recent clinical studies support combination strategies, next-generation FGFR inhibitors, and earlier use of FGFR-directed therapy, while emerging technologies, including artificial intelligence–assisted pathology and integrated multi-omic biomarkers, may further improve patient selection. Conclusions and Relevance FGFR alterations have become integral to the molecular classification and precision management of UC. Continued advances in molecular diagnostics, liquid biopsy, biomarker-guided therapy, and next-generation FGFR inhibitors are expected to further personalize care. This review provides a practical framework for integrating FGFR biomarkers into contemporary management and highlights emerging developments likely to influence future clinical practice.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"86 1 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293042","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":"Long-Term Outcomes of De-Escalated 30-Gy Elective Irradiation in HPV-Associated Oropharyngeal Cancer","authors":"Amir H. Safavi, E. Christopher Dee, C. Jillian Tsai, Yingzhi Wu, Sean M. McBride, Daphna Y. Gelblum, Yao Yu, Linda C. Chen, Kaveh Zakeri, Achraf Shamseddine, Jung J. Kang, Hannah Joy, Allison Sheih, Diana Roth O’Brien, Jennifer R. Cracchiolo, Richard J. Wong, Marc A. Cohen, Ian Ganly, Lara A. Dunn, Alan L. Ho, Eric J. Sherman, Nadeem Riaz, Nancy Y. Lee","doi":"10.1001/jamaoncol.2026.4014","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.4014","url":null,"abstract":"This cohort study describes 5-year outcomes following a de-escalated 30-Gy elective nodal irradiation regimen during definitive concurrent chemoradiotherapy among patients with human papillomavirus–associated oropharyngeal carcinoma.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"1 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229884","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":"Nivolumab-Ipilimumab for Localized Microsatellite Instability–High Gastric/Gastroesophageal Junction Adenocarcinoma","authors":"Thomas Samaille, Julie Henriques, David Tougeron, Guillaume Piessen, Christelle de la Fouchardière, Christophe Louvet, Antoine Adenis, Marine Jary, Marie-Line Garcia-Larnicol, Romain Cohen, Dewi Vernerey, Jeremie H. Lefevre, Magali Svrcek, Thierry André","doi":"10.1001/jamaoncol.2026.4162","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.4162","url":null,"abstract":"Importance Neoadjuvant nivolumab plus ipilimumab in localized deficient mismatch repair/microsatellite instability–high gastric or gastroesophageal junction (GEJ) adenocarcinoma was evaluated in the NEONIPIGA study. The primary end point of pathological complete response (pCR) was previously reported. Objective To report long-term follow-up results and secondary end points, including event-free survival (EFS) and overall survival (OS), of the NEONIPIGA study. Design, Setting, and Participants The NEONIPIGA study is a French, multicenter, single-arm, phase 2 nonrandomized clinical trial that included patients with histologically proven cT2-T4NXM0 deficient mismatch repair/microsatellite instability–high GEJ adenocarcinoma who were eligible for surgery. Patients were enrolled between October 23, 2019, and June 4, 2021, and the database was locked on November 13, 2025. Intervention Neoadjuvant nivolumab, 240 mg, every 2 weeks for 6 cycles plus ipilimumab, 1 mg/kg, every 6 weeks for 2 cycles, followed by surgery 5 weeks after the last nivolumab dose, and adjuvant nivolumab, 480 mg, every 4 weeks for 9 cycles. Main Outcomes and Measures EFS and OS. Results A total of 32 patients (median [range] age, 65 [40-80] years; 8 [28%] female and 21 [72%] were male) were included: 16 (50%) with gastric cancer and 16 (50%) with GEJ cancer. Three patients did not undergo surgery (1 with metastatic disease and 2 who refused). Twenty-seven patients (84%) completed neoadjuvant therapy and 14 (44%) received all treatment as planned. Neoadjuvant and adjuvant therapy-related grade 3/4 adverse events occurred in 6 (19%) and 4 patients (17%), respectively. Median follow-up was 48.3 months (95% CI, 44.8-52.0 months). Among the 32 patients in the intention-to-treat population, 4-year OS was 84.1% (95% CI, 65.8%-93.0%). In the 31 patients eligible for surgery, 4-year EFS was 83.5% (95% CI, 64.8%-92.8%). One patient relapsed with cerebral metastases. Six deaths occurred: 2 related to gastric cancer or treatment (1 patient had postoperative complications and 1 cerebral metastases) and 4 unrelated. All patients who did not undergo surgery achieved a clinical complete response after immune checkpoint inhibitor therapy. One patient subsequently died of causes unrelated to their cancer. Overall, 17 of 29 patients (59%) achieved pCR on surgical specimen. Safety was previously reported, and no additional late toxic effects were observed. Conclusions and Relevance In this phase 2 nonrandomized clinical trial, the immunotherapy regimen evaluated was associated with sustained long-term survival, but no clear evidence of improved survival over outcomes reported in other studies evaluating surgery alone in this patient population was observed. The high pCR rates and durable responses observed may provide useful information for designing future clinical studies, including randomized trials investigating organ-preserving strategies. Trial Registration ClinicalTrials.gov Identifier: &lt;jats:e","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"5 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187866","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":"Neoadjuvant Stereotactic Ablative Radiotherapy Before Inferior Vena Cava Thrombectomy for Renal Cell Carcinoma","authors":"Raquibul Hannan, Lin Lin, Ryan Assadi, Laurentiu M. Pop, Lily Robles, Faya Zhang, Oscar Mulvaney, Ang Gao, Payal Kapur, Ivan Pedrosa, Aurelie Garant, Daniel Yang, Chul Ahn, Michael Wait, Robert Timmerman, Vitaly Margulis","doi":"10.1001/jamaoncol.2026.4172","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.4172","url":null,"abstract":"Importance Renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus is associated with substantial perioperative risk and frequent recurrence despite nephrectomy and thrombectomy. No established neoadjuvant local therapy exists for this high-risk population. Objective To evaluate the feasibility, safety, clinical outcomes, and exploratory biomarker effects of neoadjuvant stereotactic ablative radiotherapy (SABR) targeting IVC tumor thrombus before nephrectomy and thrombectomy. Design, Setting, and Participants This single-center prospective phase 2 nonrandomized clinical trial enrolled patients with newly diagnosed RCC and Mayo level II to IV IVC tumor thrombus eligible for neoadjuvant SABR and definitive surgery from July 2015 to January 2024. Data were analyzed from August 2025 to August 2026. Intervention Neoadjuvant SABR to the radiographically defined IVC tumor thrombus, delivered as 40 Gy in 5 fractions or 36 Gy in 3 fractions, followed by radical nephrectomy and IVC thrombectomy. Main Outcomes and Measures The primary end point was 1-year recurrence-free survival (RFS) compared with a prespecified historical surgery-alone benchmark of 55.7%. Secondary outcomes included 90-day perioperative morbidity and mortality, adverse events, pulmonary embolism, overall survival, and cancer-specific survival. Exploratory analyses included Ki-67 immunohistochemistry and tumor-informed circulating tumor DNA. Results Of 23 patients who received neoadjuvant SABR, 22 completed surgery, and 21 were included in the primary RFS analysis. Of 21 included patients, 12 (57%) were male, and the median (IQR) age was 62.5 (54.0-73.2) years. A total of 19 patients had clear-cell RCC; all tumors were grade 3 or 4, and 3 patients had metastatic disease at enrollment. At a median (range) follow-up of 108.6 (2.0-127.2) months, 1-year RFS was 71.4% (80% CI, 56.6-82.0; 95% CI, 47.2-86.0), meeting the prespecified phase 2 screening criterion based on comparison with the historical surgery-alone benchmark of 55.7% ( &lt;jats:italic&gt;P&lt;/jats:italic&gt; = .09). One-year overall survival was 95.2% (80% CI, 83.9-98.7; 95% CI, 70.7-99.3) and cancer-specific survival was 95.2% (80% CI, 83.9-98.7; 95% CI, 70.7-99.3). No 90-day perioperative mortality occurred; 4 grade 4 treatment-attributed events occurred, but no grade 4/5 radiation-attributed toxic effects occurred. Ki-67 expression was reduced in patients with irradiated tumor thrombus compared with nonirradiated controls. Tumor-informed circulating tumor DNA was detected in all patients with available plasma and declined after treatment. Conclusions and Relevance In this nonrandomized clinical trial, neoadjuvant SABR before nephrectomy and IVC thrombectomy appeared feasible with an acceptable safety profile. RFS met the prespecified phase 2 screening criterion but remains exploratory and warrants further evaluation. Trial Registration ClinicalTrials.gov Identifier: &lt;jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"59 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187864","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":"Beyond Tumor Size, Toward Meaningful Patient Outcomes—Resisting RECIST","authors":"Chadi Nabhan, Vivek Subbiah","doi":"10.1001/jamaoncol.2026.3869","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.3869","url":null,"abstract":"This Viewpoint evaluates the present relevance of Response Evaluation Criteria in Solid Tumors (RECIST) as cancer therapeutics have evolved beyond cytotoxic chemotherapy in assessing treatment outcomes.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"407 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124115","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":"Disitamab Vedotin Plus Tislelizumab in Transurethrally Unresectable, ERBB2 -Positive, Non–Muscle-Invasive Bladder Cancer","authors":"Yunkai Qie, Kaipeng Jia, Shiwang Huang, Jiazeng Zhao, Zihan Xue, Shizheng Guo, Tianxiao Zhang, Zhouliang Wu, Chong Shen, Hailong Hu","doi":"10.1001/jamaoncol.2026.3909","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.3909","url":null,"abstract":"Importance Very high-risk non–muscle-invasive bladder cancer (VHR NMIBC) includes extensive high-grade T1 (T1HG) disease, T1HG with carcinoma in situ, variant histology, lymphovascular invasion, or bacille Calmette-Guérin (BCG)–unresponsive disease. Transurethrally unresectable disease warrants radical cystectomy, but patients ineligible for or declining cystectomy lack established nonsurgical therapy. Objective To evaluate the efficacy and safety of disitamab vedotin (DV, an anti- &lt;jats:italic&gt;ERBB2&lt;/jats:italic&gt; [formerly &lt;jats:italic&gt;HER2&lt;/jats:italic&gt; ] antibody-drug conjugate) plus tislelizumab (an anti–programmed cell death 1 protein immune checkpoint inhibitor) in transurethrally unresectable &lt;jats:italic&gt;ERBB2&lt;/jats:italic&gt; -positive VHR NMIBC. Design, Setting, and Participants This was an open-label, single-arm, phase 2, nonrandomized clinical trial with a Simon 2-stage design, conducted in an academic hospital from August 2022 to May 2024 with a median follow-up of 29.4 months. The analysis included adults with transurethrally unresectable &lt;jats:italic&gt;ERBB2&lt;/jats:italic&gt; -positive NMIBC who met the 2019 European Association of Urology VHR criteria and who were ineligible for or declined cystectomy. Intervention Patients received an intravenous injection of DV (120 mg, day 1) plus tislelizumab (200 mg, day 2) every 3 weeks for 3 cycles; patients who responded received up to 8 DV cycles and 17 tislelizumab cycles. Main Outcomes and Measures The primary outcome was complete response (CR) of high-risk disease, defined as no high-grade tumor, T1 disease, carcinoma in situ, or progression. Secondary outcomes were response duration, progression-free survival, overall survival, and safety. Results Among 137 screened patients, 28 participants (median [IQR] age, 72 [67-74] years; 25 male [89%]) were included. Two preassessment withdrawals were counted as nonresponders in the all-treated analysis, which left 26 efficacy-evaluable patients. CR of high-risk disease was achieved in 19 of 26 (73.1%; 95% CI, 54.8%-91.3%), meeting the prespecified 70% alternative-rate goal. Among all 28, 19 responded (67.9%; 95% CI, 49.4%-86.3%), exceeding the 17-response exact binomial threshold. Both analyses met the primary criterion. Among responders, the 24-month sustained response was 83.5% (95% CI, 68.0%-100.0%), and no muscle invasive or metastatic progression occurred. Treatment-related adverse events occurred in 25 patients (89.3%), most commonly paresthesia (12 [42.9%]), alopecia (11 [39.3%]), and pruritus (10 [35.7%]); 4 (14.3%) had grade 3 to 4 events; 2 (7.1%) discontinued treatment; and none had grade 5 events. Conclusions and Relevance Findings of this nonrandomized clinical trial suggest that DV plus tislelizumab may show a high CR rate and durable disease control in patients with transurethrally unresectable &lt;jats:italic&gt;ERBB2&lt;/jats:italic&gt; -positive VHR NMIBC, supporting randomized clinical trials. Trial Registration ClinicalTrials.gov Identifier: &lt;j","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"38 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124116","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":"Rethinking Value in Cancer Care in the US","authors":"Chirag Shah","doi":"10.1001/jamaoncol.2026.3866","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.3866","url":null,"abstract":"This Viewpoint aims to provide an understanding of the current contrast in reimbursement for cancer treatment modalities in the US.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"1 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088318","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":"Rethinking Treatment Intensification in Poorly Chemosensitive Ovarian Cancer","authors":"Benoit You, Andrew Clamp, Kathleen N. Moore, Stephanie Lheureux, Ilan Bruchim, Pauline Corbaux, Hyun-Woong Cho, Maria del Pilar Estevez-Diz, Gilles Freyer, Rosalind M. Glasspool, Antonio González-Martín, Charlie Gourley, Philipp Harter, Judith R. Kroep, Alexandra Leary, Myong Cheol Lim, Domenica Lorusso, Claudia Marchetti, Christian Marth, Bradley J. Monk, Robert D. Morgan, Asima Mukhopadhyay, Alexander B. Olawaiye, Gabriella Maria Parma, Marc-Edy Pierre, Ka Yu Tse, Nozomu Yanaihara, Isabelle Ray-Coquard","doi":"10.1001/jamaoncol.2026.3875","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.3875","url":null,"abstract":"Importance Despite the integration of bevacizumab and poly(ADP-ribose) polymerase inhibitors into first-line treatment of advanced high-grade serous ovarian cancer, survival remains poor for the substantial subset of patients whose tumors respond insufficiently to platinum-based chemotherapy and who, therefore, frequently do not achieve complete cytoreductive surgery (the 2 red flags population). This Review examines the rationale, current evidence, and emerging strategies for systemic treatment intensification—or chemosensitization—aimed at improving tumor response before initiating maintenance therapy. Observations Achieving minimal residual disease before maintenance depends on 2 key determinants: surgical completeness and intrinsic tumor chemosensitivity. Pragmatic indicators of chemosensitivity—KELIM (modeled cancer antigen 125 elimination rate constant K), pathological chemotherapy response score, and radiologic response—are now cited in European Society for Medical Oncology–European Society of Gynaecological Oncology and American Society of Clinical Oncology guidelines, while <jats:italic toggle=\"yes\">BRCA</jats:italic> /homologous recombination deficiency status may not reliably predict neoadjuvant carboplatin-paclitaxel response. Across post hoc analyses of phase 3 trials (ICON-7, GOG-0218, ICON-8, ICON-8B, VELIA, and IMagyn050), patients with poorly chemosensitive disease may have derived greater benefit from intensification strategies. Weekly dose-dense paclitaxel was associated with improved survival in the 2 red flags subgroup of ICON-8. Bevacizumab, added either to standard postoperative chemotherapy or to neoadjuvant dose-dense chemotherapy, showed signals of greater benefit on both progression-free and overall survival in high-risk and poorly chemosensitive subsets. In contrast, poly(ADP-ribose) polymerase inhibitor and immune checkpoint inhibitor combinations showed meaningful activity only in selected subgroups, supporting further evaluation of innovative DNA repair–targeting agents and immunotherapeutic approaches in these populations. Conclusions and Relevance Early identification of poorly chemosensitive advanced high-grade serous ovarian cancer enables a response-adapted first-line strategy in which treatment intensification is selectively offered to patients most likely to benefit—an approach now being prospectively evaluated in the phase 3 SALVOVAR and phase 1/2 RegeNovar trials. This framework provides a clinically actionable platform to test novel therapies aimed at increasing complete interval cytoreduction rates and improving survival in a population with otherwise limited options.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"18 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083857","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":"Actionable Signals in Pancreatic Cancer Risk Scores—Reply","authors":"Jie Ding,Michael Hoffmeister","doi":"10.1001/jamaoncol.2026.3805","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.3805","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087939","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}