Pub Date : 2025-12-11DOI: 10.1001/jamaoncol.2025.5220
Irene M. Kang, Jamie K. Forschmiedt, Michelle M. Loch, Danika L. Lew, William E. Barlow, Julie R. Gralow, Funda Meric-Bernstam, Kathy S. Albain, Daniel F. Hayes, Nancy U. Lin, Edith A. Perez, Lori J. Goldstein, Priya Rastogi, Anne F. Schott, Rick Baehner, Priyanka Sharma, Debasish Tripathy, Lajos Pusztai, Gabriel N. Hortobagyi, Kevin Kalinsky, N. Lynn Henry
Importance Breast cancer treatment is associated with cancer-related cognitive impairment (CRCI). However, the association of endocrine therapy (ET) vs chemotherapy plus endocrine therapy (CET) with CRCI is poorly understood. Objective To compare patient-reported CRCI between women with breast cancer treated with ET vs CET and to consider whether menopausal status may be associated. Design, Settings, and Participants This was a prespecified secondary analysis of RxPONDER (SWOG S1007), a multinational phase 3 randomized clinical trial of more than 5000 women with hormone receptor−positive <jats:italic>ERBB2</jats:italic> -negative (formerly <jats:italic>HER2</jats:italic> -negative) breast cancer with 1 to 3 involved lymph nodes and Oncotype DX (21-gene recurrence score) of 25 or less. Participants were enrolled from February 2011 to September 2017, with results first reported in December 2020. Participants were randomly assigned to CET or ET, with ongoing follow-up. This secondary analysis assessed cognitive function using the Patient-Reported Outcomes Measurement Information System Perceived Cognitive Function Concerns (PCF) questionnaire at baseline, 6, 12, and 36 months. Data were analyzed from July 2022 to August 2025. Intervention Random assignment to CET or ET. Main Outcomes and Measures Mean PCF standardized (T) scores by menopausal status over time using generalized estimating equations analysis for continuous outcomes. Results Of the 568 patients who completed the baseline questionnaire and were included in the analysis, 139 (24%) were premenopausal (median [range] age, 47.8 [28.0-56.3] years) and 429 (76%) were postmenopausal (median [range] age, 62.3 [37.3-87.6] years). Among the 274 (48%) who received CET and the 294 (52%) who received ET alone, CET was determined to have a greater negative association with patient-reported CRCI in both the pre- and postmenopausal participants during the 36-month follow-up. In the ET alone group, PCF scores for premenopausal participants decreased from baseline to 6 and 12 months (53.53, 51.51, and 51.72, respectively) but recovered to baseline (54.36) at 36 months. For postmenopausal participants, mean PCF scores were essentially stable (51.72, 51.13, 51.11, and 51.70, respectively); however, in the CET group, PCF scores for both pre- and postmenopausal participants decreased from baseline to 6 and 12 months (premenopausal, 52.84, 49.27, 48.04; postmenopausal, 50.65, 48.39, 47.13, respectively) and did not return to baseline at 36 months (premenopausal, 49.25; postmenopausal, 48.44). The difference in longitudinal mean PCF scores over time between CET and ET groups was −3.02 (95% CI, −5.33 to −0.72; <jats:italic>P</jats:italic> = .01) for premenopausal and −2.37 (95% CI, −3.92 to −0.82; <jats:italic>P</jats:italic> = .003) for postmenopausal participants. Conclusions and Relevance This secondary analysis of the RxPONDER found that CET had a greater negative association with patient-reported CRCI comp
{"title":"Cognitive Impairment and Chemoendocrine vs Endocrine Therapy in Pre- and Postmenopausal Women","authors":"Irene M. Kang, Jamie K. Forschmiedt, Michelle M. Loch, Danika L. Lew, William E. Barlow, Julie R. Gralow, Funda Meric-Bernstam, Kathy S. Albain, Daniel F. Hayes, Nancy U. Lin, Edith A. Perez, Lori J. Goldstein, Priya Rastogi, Anne F. Schott, Rick Baehner, Priyanka Sharma, Debasish Tripathy, Lajos Pusztai, Gabriel N. Hortobagyi, Kevin Kalinsky, N. Lynn Henry","doi":"10.1001/jamaoncol.2025.5220","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5220","url":null,"abstract":"Importance Breast cancer treatment is associated with cancer-related cognitive impairment (CRCI). However, the association of endocrine therapy (ET) vs chemotherapy plus endocrine therapy (CET) with CRCI is poorly understood. Objective To compare patient-reported CRCI between women with breast cancer treated with ET vs CET and to consider whether menopausal status may be associated. Design, Settings, and Participants This was a prespecified secondary analysis of RxPONDER (SWOG S1007), a multinational phase 3 randomized clinical trial of more than 5000 women with hormone receptor−positive <jats:italic>ERBB2</jats:italic> -negative (formerly <jats:italic>HER2</jats:italic> -negative) breast cancer with 1 to 3 involved lymph nodes and Oncotype DX (21-gene recurrence score) of 25 or less. Participants were enrolled from February 2011 to September 2017, with results first reported in December 2020. Participants were randomly assigned to CET or ET, with ongoing follow-up. This secondary analysis assessed cognitive function using the Patient-Reported Outcomes Measurement Information System Perceived Cognitive Function Concerns (PCF) questionnaire at baseline, 6, 12, and 36 months. Data were analyzed from July 2022 to August 2025. Intervention Random assignment to CET or ET. Main Outcomes and Measures Mean PCF standardized (T) scores by menopausal status over time using generalized estimating equations analysis for continuous outcomes. Results Of the 568 patients who completed the baseline questionnaire and were included in the analysis, 139 (24%) were premenopausal (median [range] age, 47.8 [28.0-56.3] years) and 429 (76%) were postmenopausal (median [range] age, 62.3 [37.3-87.6] years). Among the 274 (48%) who received CET and the 294 (52%) who received ET alone, CET was determined to have a greater negative association with patient-reported CRCI in both the pre- and postmenopausal participants during the 36-month follow-up. In the ET alone group, PCF scores for premenopausal participants decreased from baseline to 6 and 12 months (53.53, 51.51, and 51.72, respectively) but recovered to baseline (54.36) at 36 months. For postmenopausal participants, mean PCF scores were essentially stable (51.72, 51.13, 51.11, and 51.70, respectively); however, in the CET group, PCF scores for both pre- and postmenopausal participants decreased from baseline to 6 and 12 months (premenopausal, 52.84, 49.27, 48.04; postmenopausal, 50.65, 48.39, 47.13, respectively) and did not return to baseline at 36 months (premenopausal, 49.25; postmenopausal, 48.44). The difference in longitudinal mean PCF scores over time between CET and ET groups was −3.02 (95% CI, −5.33 to −0.72; <jats:italic>P</jats:italic> = .01) for premenopausal and −2.37 (95% CI, −3.92 to −0.82; <jats:italic>P</jats:italic> = .003) for postmenopausal participants. Conclusions and Relevance This secondary analysis of the RxPONDER found that CET had a greater negative association with patient-reported CRCI comp","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"94 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717268","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}
Pub Date : 2025-12-11DOI: 10.1001/jamaoncol.2025.5629
{"title":"Error in Denominator in Results Text.","authors":"","doi":"10.1001/jamaoncol.2025.5629","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5629","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"15 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717876","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":"Stroke in Patients With Cancer-Time Is Brain.","authors":"Ronda Lun,Jeffrey Q Cao,Andrew Demchuk,Umberto Pensato","doi":"10.1001/jamaoncol.2025.5234","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5234","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"145 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717874","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}
Pub Date : 2025-12-11DOI: 10.1001/jamaoncol.2025.5088
Michelle C Janelsins,Allison Magnuson
{"title":"Unraveling the Complexity of Cancer-Related Cognitive Impairment in Breast Cancer-Effect of Differing Treatments and Menopausal Status.","authors":"Michelle C Janelsins,Allison Magnuson","doi":"10.1001/jamaoncol.2025.5088","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5088","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"35 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717877","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}
Pub Date : 2025-12-11DOI: 10.1001/jamaoncol.2025.5241
Nikhil P. Mankuzhy, Fan Yang, Lillian A. Boe, Chengcheng Gui, Yingzhi Wu, Nadeem Riaz, Yao Yu, Sean M. McBride, Achraf Shamseddine, Andy Shim, Dennis Mah, Lara A. Dunn, Loren S. Michel, David G. Pfister, Eric J. Sherman, Ian Ganly, Jennifer R. Cracchiolo, Snehal G. Patel, Richard J. Wong, Marc A. Cohen, Nancy Y. Lee
This cohort study evaluates the use of definitive rhinectomy and adjuvant radiotherapy with or without chemotherapy for patients who declined rhinectomy or had unresectable disease.
{"title":"Organ Preservation for Nasal Cavity Cancers Using Definitive Radiotherapy for Avoiding Rhinectomy","authors":"Nikhil P. Mankuzhy, Fan Yang, Lillian A. Boe, Chengcheng Gui, Yingzhi Wu, Nadeem Riaz, Yao Yu, Sean M. McBride, Achraf Shamseddine, Andy Shim, Dennis Mah, Lara A. Dunn, Loren S. Michel, David G. Pfister, Eric J. Sherman, Ian Ganly, Jennifer R. Cracchiolo, Snehal G. Patel, Richard J. Wong, Marc A. Cohen, Nancy Y. Lee","doi":"10.1001/jamaoncol.2025.5241","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5241","url":null,"abstract":"This cohort study evaluates the use of definitive rhinectomy and adjuvant radiotherapy with or without chemotherapy for patients who declined rhinectomy or had unresectable disease.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717267","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}
Pub Date : 2025-12-04DOI: 10.1001/jamaoncol.2025.5144
George Q Zhang,Jeffrey A Meyerhardt,Qian Shi,Tyler Twombly,Levi Pederson,Chao Ma,Juha P Väyrynen,Melissa Zhao,Yasutoshi Takashima,Ardaman Shergill,Pankaj Kumar,Felix Couture,Philip Kuebler,Smitha Krishnamurthi,Benjamin Tan,Eileen M O'Reilly,Marios Giannakis,Shuji Ogino,Adham Jurdi,Shruti Sharma,Alexey Aleshin,Anthony F Shields,Jonathan A Nowak
ImportanceObservational studies have associated use of aspirin and selective cyclooxygenase inhibitors with decreased recurrence and improved survival in patients with colon cancer. While randomized clinical trials have not shown benefit across all patients, these findings suggest that select subgroups may benefit from their use. Despite the well-established prognostic value of circulating tumor DNA (ctDNA), its role in guiding treatment remains unclear.ObjectiveTo investigate the predictive value of postoperative ctDNA for survival outcomes with adjuvant celecoxib alongside conventional chemotherapy in patients with stage III colon cancer.Design, Setting, and ParticipantsThis was a post hoc analysis of the phase 3 Cancer and Leukemia Group B (now Alliance)/Southwest Oncology Group 80702 randomized clinical trial (2010-2015) assessing adjuvant celecoxib vs placebo and 3 vs 6 months of adjuvant 5-fluorouracil, leucovorin, and oxaliplatin for stage III colon cancer. Patients consented to biospecimen collection and had ctDNA analysis performed. Data analysis was performed from September 2024 to June 2025.ExposuresPostoperative ctDNA positivity was determined using a clinically validated, tumor-informed 16-plex-polymerase chain reaction-next-generation sequencing assay (Signatera; Natera Inc) performed between surgery and initiation of adjuvant therapy.Main Outcomes and MeasuresDisease-free survival (DFS) and overall survival (OS). Survival by ctDNA status and adjuvant celecoxib use were assessed as part of a post hoc companion study with prespecified statistical analysis plan.ResultsAmong 940 patients (mean [SD] age, 60.9 [10.8] years; 426 female [45.3%] and 515 male [54.7%] individuals; 222 [23.6%] with prior low-dose aspirin use; and median follow-up of 6.0 [95% CI, 6.0-6.0] years), 767 (81.6%) were ctDNA negative and 173 (18.4%) were ctDNA positive. ctDNA positivity was highly prognostic of worse DFS (reference, ctDNA negativity; adjusted hazard ratio [aHR], 6.12; 95% CI, 4.66-8.03) and OS (aHR, 5.86; 95% CI, 4.19-8.19). In patients with ctDNA positivity, celecoxib was associated with improved DFS (aHR, 0.61; 95% CI, 0.42-0.89) and OS (aHR, 0.62; 95% CI, 0.40-0.96) compared to placebo. Among patients with ctDNA negativity, celecoxib did not provide survival benefit (DFS: aHR, 0.76; 95% CI, 0.53-1.09; OS: aHR, 0.85; 95% CI, 0.54-1.36), although the interaction was not significant (P for interaction, .41 and .33 for DFS and OS, respectively). These findings persisted when stratifying patients by microsatellite instability status and PIK3CA mutational status.Conclusion and RelevanceThe findings of this post hoc analysis suggest that ctDNA status has the potential to inform clinical decision-making among patients with stage III colon cancer who should consider adjuvant celecoxib in addition to conventional chemotherapy.Trial RegistrationClinicalTrials.gov Identifier: NCT01150045.
{"title":"Predictive Role of Circulating Tumor DNA in Stage III Colon Cancer Treated With Celecoxib: A Post Hoc Analysis of the CALGB (Alliance)/SWOG 80702 Phase 3 Randomized Clinical Trial.","authors":"George Q Zhang,Jeffrey A Meyerhardt,Qian Shi,Tyler Twombly,Levi Pederson,Chao Ma,Juha P Väyrynen,Melissa Zhao,Yasutoshi Takashima,Ardaman Shergill,Pankaj Kumar,Felix Couture,Philip Kuebler,Smitha Krishnamurthi,Benjamin Tan,Eileen M O'Reilly,Marios Giannakis,Shuji Ogino,Adham Jurdi,Shruti Sharma,Alexey Aleshin,Anthony F Shields,Jonathan A Nowak","doi":"10.1001/jamaoncol.2025.5144","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5144","url":null,"abstract":"ImportanceObservational studies have associated use of aspirin and selective cyclooxygenase inhibitors with decreased recurrence and improved survival in patients with colon cancer. While randomized clinical trials have not shown benefit across all patients, these findings suggest that select subgroups may benefit from their use. Despite the well-established prognostic value of circulating tumor DNA (ctDNA), its role in guiding treatment remains unclear.ObjectiveTo investigate the predictive value of postoperative ctDNA for survival outcomes with adjuvant celecoxib alongside conventional chemotherapy in patients with stage III colon cancer.Design, Setting, and ParticipantsThis was a post hoc analysis of the phase 3 Cancer and Leukemia Group B (now Alliance)/Southwest Oncology Group 80702 randomized clinical trial (2010-2015) assessing adjuvant celecoxib vs placebo and 3 vs 6 months of adjuvant 5-fluorouracil, leucovorin, and oxaliplatin for stage III colon cancer. Patients consented to biospecimen collection and had ctDNA analysis performed. Data analysis was performed from September 2024 to June 2025.ExposuresPostoperative ctDNA positivity was determined using a clinically validated, tumor-informed 16-plex-polymerase chain reaction-next-generation sequencing assay (Signatera; Natera Inc) performed between surgery and initiation of adjuvant therapy.Main Outcomes and MeasuresDisease-free survival (DFS) and overall survival (OS). Survival by ctDNA status and adjuvant celecoxib use were assessed as part of a post hoc companion study with prespecified statistical analysis plan.ResultsAmong 940 patients (mean [SD] age, 60.9 [10.8] years; 426 female [45.3%] and 515 male [54.7%] individuals; 222 [23.6%] with prior low-dose aspirin use; and median follow-up of 6.0 [95% CI, 6.0-6.0] years), 767 (81.6%) were ctDNA negative and 173 (18.4%) were ctDNA positive. ctDNA positivity was highly prognostic of worse DFS (reference, ctDNA negativity; adjusted hazard ratio [aHR], 6.12; 95% CI, 4.66-8.03) and OS (aHR, 5.86; 95% CI, 4.19-8.19). In patients with ctDNA positivity, celecoxib was associated with improved DFS (aHR, 0.61; 95% CI, 0.42-0.89) and OS (aHR, 0.62; 95% CI, 0.40-0.96) compared to placebo. Among patients with ctDNA negativity, celecoxib did not provide survival benefit (DFS: aHR, 0.76; 95% CI, 0.53-1.09; OS: aHR, 0.85; 95% CI, 0.54-1.36), although the interaction was not significant (P for interaction, .41 and .33 for DFS and OS, respectively). These findings persisted when stratifying patients by microsatellite instability status and PIK3CA mutational status.Conclusion and RelevanceThe findings of this post hoc analysis suggest that ctDNA status has the potential to inform clinical decision-making among patients with stage III colon cancer who should consider adjuvant celecoxib in addition to conventional chemotherapy.Trial RegistrationClinicalTrials.gov Identifier: NCT01150045.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"19 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664048","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}
Pub Date : 2025-12-04DOI: 10.1001/jamaoncol.2025.3644
Atulya Aman Khosla,Neil Mendhiratta,Karan Jatwani
{"title":"Urinary Diversion After Cystectomy for Bladder Cancer.","authors":"Atulya Aman Khosla,Neil Mendhiratta,Karan Jatwani","doi":"10.1001/jamaoncol.2025.3644","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.3644","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"115 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664049","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}
Pub Date : 2025-12-04DOI: 10.1001/jamaoncol.2025.5061
David A Drew,Philip E Castle
{"title":"Tailored COX-2 Inhibition for Precision Adjuvant Therapy of Localized Metastatic Colon Cancer.","authors":"David A Drew,Philip E Castle","doi":"10.1001/jamaoncol.2025.5061","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5061","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"115 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664224","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}
Pub Date : 2025-11-26DOI: 10.1001/jamaoncol.2025.5094
Francesco Sclafani,Vincent Staggs,Everardo D Saad
{"title":"Clarifying End Point Definitions, Missingness, and Covariate Balance in the International TNT Study-Reply.","authors":"Francesco Sclafani,Vincent Staggs,Everardo D Saad","doi":"10.1001/jamaoncol.2025.5094","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5094","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"98 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600019","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}
Pub Date : 2025-11-26DOI: 10.1001/jamaoncol.2025.5097
Beung Chul Ahn,Yu Jung Kim,Youngjoo Lee,Koung Jin Suh,Se Hyun Kim,Dong-Wan Kim,Tae Min Kim,Ki Hyeong Lee,Ji-Youn Han
ImportanceROS1 rearrangement is rare but is an attractive therapeutic target in advanced non-small cell lung cancer (NSCLC). Crizotinib, entrectinib, and repotrectinib have been approved by the US Food and Drug Administration for treatment of ROS1-positive NSCLC. Lorlatinib, a brain-penetrant, third-generation tyrosine kinase inhibitor (TKI), targets ROS1 and ALK; however, its efficacy and safety for patients with advanced ROS1-positive remains unknown.ObjectiveTo evaluate the efficacy and safety of lorlatinib for patients with advanced ROS1-positive NSCLC never treated with any TKI.Design, Setting, and ParticipantsThis multicenter phase 2 nonrandomized clinical trial enrolled patients with advanced ROS1-positive NSCLC who were TKI-naive with an Eastern Cooperative Oncology Group performance status of 2 or less, and 1 or no prior platinum-based chemotherapy. Participants were recruited from June 2019 to April 2023 and followed up through August 2024. Data analysis was performed from April 5 to August 30, 2025.InterventionsLorlatinib, 100 mg daily, was administered until disease progression, toxic effects, consent withdrawal, or death.Main Outcomes and MeasuresObjective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival, and safety.ResultsThe analysis included 32 patients (mean [IQR] age, 59 [11] years; 20 female [63%] and 12 male [37%] individuals), all of whom had adenocarcinoma histologic findings. There were 21 patients (66%) who were treatment-naive, and 11 (34%) who had prior chemotherapy. The median (SD) follow-up duration was 22.1 (15.4-46.8) months; ORR was 73% (95% CI, 56%-86%; 22 of 30 patients), and disease control rate was 90% (95% CI, 74%-97%; 27 of 30 patients). Median (IQR) PFS was 53.6 (95% CI, 27.8-79.5) months, and overall survival was not reached. For treatment-naive vs previously treated patients, the ORR was 90% vs 60%, and PFS was not reached vs 35.8 months. Grade 3 to 4 adverse effects were hypertriglyceridemia (5 patients [16%]) and hypercholesterolemia (8 patients [25%]). No treatment-related deaths occurred.Conclusions and RelevanceIn this nonrandomized clinical trial, lorlatinib demonstrated durable efficacy and manageable safety in TKI-naive advanced ROS1-positive NSCLC, supporting the potential for using lorlatinib in earlier treatment settings.Trial RegistrationClinicalTrials.gov Identifier: NCT03612154.
{"title":"Lorlatinib in Tyrosine Kinase Inhibitor-Naive Advanced ROS1-Positive Non-Small Cell Lung Cancer: A Phase 2 Nonrandomized Clinical Trial.","authors":"Beung Chul Ahn,Yu Jung Kim,Youngjoo Lee,Koung Jin Suh,Se Hyun Kim,Dong-Wan Kim,Tae Min Kim,Ki Hyeong Lee,Ji-Youn Han","doi":"10.1001/jamaoncol.2025.5097","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5097","url":null,"abstract":"ImportanceROS1 rearrangement is rare but is an attractive therapeutic target in advanced non-small cell lung cancer (NSCLC). Crizotinib, entrectinib, and repotrectinib have been approved by the US Food and Drug Administration for treatment of ROS1-positive NSCLC. Lorlatinib, a brain-penetrant, third-generation tyrosine kinase inhibitor (TKI), targets ROS1 and ALK; however, its efficacy and safety for patients with advanced ROS1-positive remains unknown.ObjectiveTo evaluate the efficacy and safety of lorlatinib for patients with advanced ROS1-positive NSCLC never treated with any TKI.Design, Setting, and ParticipantsThis multicenter phase 2 nonrandomized clinical trial enrolled patients with advanced ROS1-positive NSCLC who were TKI-naive with an Eastern Cooperative Oncology Group performance status of 2 or less, and 1 or no prior platinum-based chemotherapy. Participants were recruited from June 2019 to April 2023 and followed up through August 2024. Data analysis was performed from April 5 to August 30, 2025.InterventionsLorlatinib, 100 mg daily, was administered until disease progression, toxic effects, consent withdrawal, or death.Main Outcomes and MeasuresObjective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival, and safety.ResultsThe analysis included 32 patients (mean [IQR] age, 59 [11] years; 20 female [63%] and 12 male [37%] individuals), all of whom had adenocarcinoma histologic findings. There were 21 patients (66%) who were treatment-naive, and 11 (34%) who had prior chemotherapy. The median (SD) follow-up duration was 22.1 (15.4-46.8) months; ORR was 73% (95% CI, 56%-86%; 22 of 30 patients), and disease control rate was 90% (95% CI, 74%-97%; 27 of 30 patients). Median (IQR) PFS was 53.6 (95% CI, 27.8-79.5) months, and overall survival was not reached. For treatment-naive vs previously treated patients, the ORR was 90% vs 60%, and PFS was not reached vs 35.8 months. Grade 3 to 4 adverse effects were hypertriglyceridemia (5 patients [16%]) and hypercholesterolemia (8 patients [25%]). No treatment-related deaths occurred.Conclusions and RelevanceIn this nonrandomized clinical trial, lorlatinib demonstrated durable efficacy and manageable safety in TKI-naive advanced ROS1-positive NSCLC, supporting the potential for using lorlatinib in earlier treatment settings.Trial RegistrationClinicalTrials.gov Identifier: NCT03612154.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"29 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600022","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}
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