Journal of Clinical Oncology最新文献

{"title":"Phase I Study of 131I-Metaiodobenzylguanidine With Dinutuximab ± Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy Trial.","authors":"Thomas Cash,Araz Marachelian,Steven G DuBois,Yueh-Yun Chi,Anahit Baregamyan,Susan G Groshen,Hunter C Jonus,Anasheh Shamirian,Mary Crowley,Fariba Goodarzian,Patricia T Acharya,Bruce Pawel,Amy K Erbe,Ankita Shahi,Jen Zaborek,Eleanor Kennedy,Shahab Asgharzadeh,Judith G Villablanca,Navin Pinto,Brian D Weiss,Yael P Mosse,Ami V Desai,Margaret E Macy,Meaghan Granger,Kieuhoa T Vo,Paul M Sondel,Katherine K Matthay,Julie R Park,Kelly C Goldsmith","doi":"10.1200/jco-24-02612","DOIUrl":"https://doi.org/10.1200/jco-24-02612","url":null,"abstract":"PURPOSEWe conducted a phase I trial to determine the safety, tolerability, and preliminary antitumor activity of 131I-metaiodobenzylguanidine (MIBG) combined with the anti-GD2 antibody dinutuximab with or without the histone deacetylase inhibitor vorinostat in patients with relapsed/refractory neuroblastoma (rNBL).METHODSIn part A, patients with MIBG-avid rNBL received MIBG intravenously (IV) on day 1 at 12, 15, or 18 mCi/kg per the rolling six design and dinutuximab (17.5 mg/m2 once daily) IV on days 8-11 and 29-32 and granulocyte-macrophage colony-stimulating factor (250 mcg/m2 once daily) subcutaneously on days 8-17 and 29-38. Autologous stem cells were infused on day 15. In part B, vorinostat at 180 mg/m2 once daily was given orally on days 0-13 in combination with the part A recommended phase II dose (RP2D). Patients could receive two courses.RESULTSForty-five eligible patients enrolled, of whom 31 were evaluable. The median age was 7.5 (range, 2.9-24.1) years. For part A (n = 19), no dose-limiting toxicities (DLTs) occurred across all dose levels and courses, establishing the RP2D of MIBG to be 18 mCi/kg. In part B (n = 12), 1 DLT (grade 3 hypokalemia) occurred during course 1, and 3 of 11 patients who received a second course experienced DLT: grade 3 ALT increase, grade 4 hypoxia and grade 5 pneumonitis, and grade 3 fatigue. The best overall response rate (BORR; complete response [CR] + partial response [PR]) on part A was 42% with a CR/PR/minor response (MR) rate of 46%, and 19% progressive disease (PD) rate. For part B, the BORR was 42% with a CR/PR/MR rate of 75% and 0% PD rate.CONCLUSIONMIBG combined with dinutuximab was well tolerated with encouraging antitumor activity. Vorinostat added to this combination may augment responses in this heavily pretreated patient population.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"19 1","pages":"JCO2402612"},"PeriodicalIF":45.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370172","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":"Optimizing Allogeneic Chimeric Antigen Receptor T-Cell Persistence in Relapsed/Refractory Large B-Cell Lymphoma: The Role of KIR Matching.","authors":"Yutaka Shimazu","doi":"10.1200/jco-25-00394","DOIUrl":"https://doi.org/10.1200/jco-25-00394","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"4 1","pages":"JCO2500394"},"PeriodicalIF":45.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370138","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":"Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia.","authors":"Inna M Chen, Julia S Johansen, Susann Theile, Libbie M Silverman, Katherine R Pelz, Kasper Madsen, Olav Dajani, Kevin Z M Lim, Torben Lorentzen, Omnia Gaafer, Leonidas G Koniaris, Anna C Ferreira, Brian Neelon, Denis C Guttridge, Michael C Ostrowski, Teresa A Zimmers, Dorte Nielsen","doi":"10.1200/JCO.23.01965","DOIUrl":"10.1200/JCO.23.01965","url":null,"abstract":"<p><strong>Purpose: </strong>This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).</p><p><strong>Methods: </strong>A safety cohort received Gem 1,000 mg/m² and Nab 125 mg/m² on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).</p><p><strong>Results: </strong>Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (<i>P</i> = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% <i>v</i> 7.0%, <i>P</i> = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (<i>P</i> < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (<i>P</i> = .0012) at 2 months and +0.7044 versus -3.353% (<i>P</i> = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (<i>P</i> = .0045) and 41.82% versus 68.75% (<i>P</i> = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc.</p><p><strong>Conclusion: </strong>Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2107-2118"},"PeriodicalIF":42.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002191","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":"Characteristics of Patients and Prognostic Factors Across Treatment Lines in Metastatic Colorectal Cancer: An Analysis From the Aide et Recherche en Cancérologie Digestive Database.","authors":"Jean-Baptiste Bachet, Aimery de Gramont, Morteza Raeisi, Manel Rakez, Richard M Goldberg, Niall C Tebbutt, Eric Van Cutsem, Daniel G Haller, J Randolph Hecht, Robert J Mayer, Stuart M Lichtman, Al B Benson, Alberto F Sobrero, Josep Tabernero, Richard Adams, John R Zalcberg, Axel Grothey, Takayuki Yoshino, Thierry André, Qian Shi, Benoist Chibaudel","doi":"10.1200/JCO-24-01968","DOIUrl":"10.1200/JCO-24-01968","url":null,"abstract":"<p><strong>Purpose: </strong>Several lines of treatment can be used sequentially in patients with metastatic colorectal cancer. We investigated the evolution of patient/tumor characteristics and their prognostic impact across treatment lines to develop an overall prognostic score (OPS).</p><p><strong>Patients and methods: </strong>Individual patient data from 48 randomized trials were analyzed. The end point was overall survival (from random assignment to death). Missing data were imputed. The complete data set was then separated into construction (80%) and validation sets (20%). The Cox's model was used to define risk groups for survival using the OPS. The discrimination capability was assessed in each treatment-line via bootstrapping to obtain optimism-corrected calibration and discrimination C-indices. Internal validation was done in the validation set.</p><p><strong>Results: </strong>A total of 37,560 patients (26,974 in first-line [1L], 7,693 in second-line [2L], and 2,893 in third-line [3L]) were analyzed. Some clinical, biological, and molecular characteristics of patients/tumors included in therapeutic trials evolve over the lines. Seven independent prognostic variables were retained in the final multivariate model common to all lines: Eastern Cooperative Oncology Group performance status, hemoglobin, platelet count, WBC/absolute neutrophil count ratio, lactate dehydrogenase, alkaline phosphatase, and the number of metastatic sites. The OPS was used to define four patient subgroups with significantly different prognoses in 1L, 2L, and 3L, separately, with adequate C-indices: 0.65, 0.66, and 0.69 in the construction set and 0.65, 0.66, and 0.68 in the validation set, respectively. The OPS was not predictive, with 3L drugs (<i>v</i> placebo) or subsequent line (2L/1L or 3L/2L) extending survival in all prognostic groups.</p><p><strong>Conclusion: </strong>The same prognostic model using practical variables can be used before all treatment lines. The OPS could better stratify patients in future clinical trials and help to therapeutic decision in routine practice.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2094-2106"},"PeriodicalIF":42.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010153","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":"Reply to: Assessing Clinical Utility of Datopotamab Deruxtecan Versus Chemotherapy for Breast Cancer.","authors":"Aditya Bardia, Barbara Pistilli, Hope Rugo","doi":"10.1200/JCO-24-02833","DOIUrl":"10.1200/JCO-24-02833","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2137-2138"},"PeriodicalIF":42.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735783","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":"Impact of Lean Body Mass-Based Oxaliplatin Dose Calculation on Neurotoxicity in Adjuvant Treatment of Stage III Colon Cancer: Results of the Phase II Randomized LEANOX Trial.","authors":"Eric Assenat,Meher Ben Abdelghani,Sophie Gourgou,Hervé Perrier,Faiza Khemissa Akouz,Romain Desgrippes,Marie-Pierre Galais,Chloé Janiszewski,Thibault Mazard,Yves Rinaldi,Côme Lepage,Raphael Tetreau,Pierre Senesse","doi":"10.1200/jco-24-02754","DOIUrl":"https://doi.org/10.1200/jco-24-02754","url":null,"abstract":"PURPOSEOxaliplatin-based adjuvant chemotherapy is used for stage III colon cancer, but may induce disabling neurotoxicity. We previously showed that the incidence of oxaliplatin-induced peripheral neurotoxicity (OIPN) is higher for oxaliplatin doses >3.09 mg per kg of lean body mass (LBM). This proof-of-concept, multicenter, randomized trial assessed whether LBM-based oxaliplatin dose adjustment reduces OIPN (ClinicalTrials.gov identifier: NCT03255434).METHODSAmong the patients with resected stage III colon cancer eligible for adjuvant leucovorin, fluorouracil, and oxaliplatin chemotherapy, those without LBM reduction received body surface area (BSA)-based oxaliplatin doses (85 mg/m2, arm 1). Patients with reduced LBM were randomly assigned (1:1) to receive BSA-based (arm 2) or LBM-based oxaliplatin doses (3.09 mg/kg LBM, arm 3). The primary end point was the percentage of patients without grade ≥2 OIPN in the first six cycles.RESULTSIn all, 33, 64, and 63 patients were enrolled in arms 1, 2, and 3, respectively (median age, 63 years; 52.5% of men; 89.3% Eastern Cooperative Oncology Group 0; 57.5% pT3; 60.6% pN1). The primary end point was achieved by 67.2% of patients in arm 3 versus 42.1% in arm 2 (P = .01). Longer grade ≥2 OIPN-free survival (hazard ratio [HR], 0.53 [95% CI, 0.34 to 0.84]; P = .01), longer time to grade ≥2 OIPN onset (P = .006), higher cumulative oxaliplatin doses without grade ≥2 OIPN (P = .044), and fewer oxaliplatin dose reductions (P < .001) were reported in arm 3. Relapse-free survival (HR, 1.05 [95% CI, 0.54 to 2.06]) and overall survival (OS; HR, 1.20 [95% CI, 0.36 to 3.92]) were similar in arms 2 and 3 (median follow-up of 38.6 months). Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 scores were better in arm 3.CONCLUSIONIn adjuvant settings for stage III colon cancer, using an LBM-based oxaliplatin dose significantly reduces OIPN and improves quality of life without affecting relapse-free survival and OS.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"32 1","pages":"JCO2402754"},"PeriodicalIF":45.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335363","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":"Rationale for Investigation of Neoadjuvant Chemoimmunotherapy Before Chemoradiation in Unresectable Stage III Non-Small Cell Lung Cancer.","authors":"Rajat Thawani, Christine M Bestvina, Everett E Vokes, Aditya Juloori","doi":"10.1200/JCO-24-02355","DOIUrl":"10.1200/JCO-24-02355","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2039-2043"},"PeriodicalIF":42.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730130","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":"Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline Rapid Recommendation Update.","authors":"Jaishri Blakeley, Nimish A Mohile, Hans Messersmith, Andrew B Lassman, David Schiff","doi":"10.1200/JCO-25-00250","DOIUrl":"10.1200/JCO-25-00250","url":null,"abstract":"<p><p><i>ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the</i> <i>ASCO Guideline Methodology Manual</i>. <i>The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).</i></p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2129-2133"},"PeriodicalIF":42.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003516","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":"Outcomes of Radium-223 and Stereotactic Ablative Radiotherapy Versus Stereotactic Ablative Radiotherapy for Oligometastatic Prostate Cancers: The RAVENS Phase II Randomized Trial.","authors":"Jarey H Wang, Alexander D Sherry, Soha Bazyar, Philip Sutera, Noura Radwan, Ryan M Phillips, Matthew P Deek, Jiayun Lu, Shirl Dipasquale, Curtiland Deville, Theodore L DeWeese, Daniel Y Song, Hao Wang, Robert F Hobbs, Reem Malek, Sara A Dudley, Stephen C Greco, Emmanuel S Antonarakis, Catherine H Marshall, Samuel Denmeade, Channing J Paller, Michael A Carducci, Kenneth J Pienta, Orhan K Oz, Matthew Ramotar, James L Leenstra, Sean S Park, Matthew C Abramowitz, Neil Desai, Alejandro Berlin, Bradley J Stish, Chad Tang, Phuoc T Tran, Ana P Kiess","doi":"10.1200/JCO-25-00131","DOIUrl":"10.1200/JCO-25-00131","url":null,"abstract":"<p><strong>Purpose: </strong>Randomized clinical trials (RCTs) have shown progression-free survival (PFS) benefits of metastasis-directed therapy (MDT) without androgen deprivation therapy for oligometastatic castration-sensitive prostate cancer (omCSPC). Most patients with bone metastatic (BM) omCSPC recur with additional bone disease after MDT. We hypothesized the BM-targeting alpha-emitter radium-223 dichloride (Ra223) could target subclinical bone disease and delay progression.</p><p><strong>Methods: </strong>This is an investigator-initiated, multicenter, open-label phase II RCT. Eligible men with recurrent omCSPC with ≥one bone metastasis (≤three on conventional imaging and/or ≤five on molecular imaging) were randomly assigned (1:1) to stereotactic ablative radiation (SABR) MDT alone or SABR MDT with Ra223 (six cycles). Primary end point was composite PFS.</p><p><strong>Results: </strong>From August 9, 2019, to March 2, 2023, 64 patients were randomly assigned, 33 to SABR MDT and 31 to SABR MDT/Ra223 balancing for key covariates. Most SABR MDT/Ra223 patients (87%) received six cycles of Ra223. The median PFS was 11.8 months with SABR MDT and 10.5 months with SABR MDT/Ra223 (adjusted hazard ratio [aHR], 1.42 [95% CI, 0.79 to 2.56]; <i>P</i> = .24). Seven patients (11%) experienced grade 3 treatment-related adverse events (no grade 4 or 5), 2 of 33 (6%) with SABR and 5 of 30 (17%) with SABR MDT/Ra223. Patients with high-risk (HiRi) pathogenic mutations in <i>ATM</i>, <i>BRCA1/2</i>, <i>RB1</i>, or <i>TP53</i> had worse PFS (HR, 5.95 [95% CI, 1.83 to 19.3]; <i>P</i> = .003). Greater T-cell receptor (TCR) unique productive rearrangements were prognostic for improved PFS independent of the treatment arm (aHR, 0.45 [95% CI, 0.21 to 0.96]; <i>P</i> = .04).</p><p><strong>Conclusion: </strong>Adding Ra223 to SABR MDT in BM omCSPC does not delay progression of disease. We provide evidence for an HiRi mutational signature and TCR repertoire as prognostic biomarkers in omCSPC treated with SABR MDT, highlighting the importance of collecting biological correlates in RCTs for omCSPC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2059-2068"},"PeriodicalIF":42.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016688","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":"Pragmatic Randomized Study of Afatinib Versus Chemotherapy for Patients With Non-Small Cell Lung Cancer With Uncommon Epidermal Growth Factor Receptor Mutations: ACHILLES/TORG1834.","authors":"Satoru Miura, Hiroshi Tanaka, Toshihiro Misumi, Hiroshige Yoshioka, Takaaki Tokito, Tatsuro Fukuhara, Yuki Sato, Yoshimasa Shiraishi, Katsuhiko Naoki, Hiroaki Akamatsu, Ou Yamaguchi, Toshihide Yokoyama, Shoichi Kuyama, Kazumi Nishino, Naoki Furuya, Takayasu Kurata, Terufumi Kato, Satoshi Ikeda, Hidehito Horinouchi, Eiki Ichihara, Masahide Mori, Yuichi Takiguchi, Kentaro Tanaka, Yasuhiro Goto, Hiroaki Okamoto","doi":"10.1200/JCO-24-02007","DOIUrl":"10.1200/JCO-24-02007","url":null,"abstract":"<p><strong>Purpose: </strong>To our knowledge, the ACHILLES/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor (<i>EGFR</i>) mutations.</p><p><strong>Methods: </strong>This randomized, open-label study was performed at 51 Japanese institutions and recruited treatment-naïve patients with nonsquamous NSCLC with uncommon <i>EGFR</i> mutations, excluding exon 20 insertions and T790M mutations. Patients were randomly assigned 2:1 to receive afatinib (30 or 40 mg orally, at the treating physician's discretion) or a combination of platinum (cisplatin or carboplatin) and pemetrexed, followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival, and safety. A prespecified interim analysis was planned to provide clinically meaningful information promptly, along with a crossover recommendation if necessary.</p><p><strong>Results: </strong>A total of 109 patients were enrolled between March 2019 and February 2023. In the interim analysis, the Data and Safety Monitoring Committee recommended early study termination. The median PFS was significantly longer in patients receiving afatinib than in those undergoing chemotherapy (10.6 <i>v</i> 5.7 months; hazard ratio, 0.421 [95% CI, 0.251 to 0.706]; <i>P</i> = .0010). ORRs to afatinib were similar across the overall population and among participants with major uncommon (G719X, L861Q, and S768I), compound, and other mutations (61.7%, 55.8%, 72.7%, and 60.0%, respectively). The most common grade 3 or higher adverse events were diarrhea, paronychia, and rash for afatinib, and appetite loss and nausea for chemotherapy.</p><p><strong>Conclusion: </strong>Afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon <i>EGFR</i> mutations.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2049-2058"},"PeriodicalIF":42.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064125","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}