Impact of select actionable genomic alterations on efficacy of neoadjuvant immunotherapy in resectable non-small cell lung cancer

作者：Nicolas Zhou, Cheuk Hong Leung, William N. William, Annikka Weissferdt, Apar Pataer, Myrna C. B. Godoy, Brett W. Carter, Frank V. Fossella, Anne S. Tsao, George R. Blumenschein, Xiuning Le, Jianjun Zhang, Ferdinandos Skoulidis, Jonathan M. Kurie, Mehmet Altan, Charles Lu, Bonnie S. Glisson, Lauren A. Byers, Yasir Y. Elamin, Reza J. Mehran, David C. Rice, Garrett L. Walsh, Wayne L. Hofstetter, Jack A. Roth, Hai T. Tran, Jia Wu, Luisa M. Solis Soto, Humam Kadara, Stephen G. Swisher, Ara A. Vaporciyan, Don L. Gibbons, Heather Lin, J. Jack Lee, John V. Heymach, Marcelo V. Negrão, Boris Sepesi, Tina Cascone · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2024 · DOI：10.1136/jitc-2024-009677 · 被引用次数：9 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Diagnosis and Treatment、Lung Cancer Treatments and Mutations

BACKGROUND: Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs. METHODS: Tumor molecular profiles were obtained from patients with stage I-IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF was defined as any progression of primary lung cancer after neoadjuvant ICI therapy in patients without surgery, radiographic and/or biopsy-proven primary lung cancer recurrence after surgery, or death from possibly treatment-related complications or from primary lung cancer since randomization. Tumors with AGAs (n=12) were compared with tumors without AGAs and non-profiled squamous cell carcinomas (non-AGAs+NP SCC, n=20). RESULTS: fusions. The median time to TF in patients with AGAs was 24.7 months (95% CI: 12.6 to 40.4), compared with not reached (95% CI: not evaluable (NE)-NE) in the non-AGAs+NP SCC group. The TF risk was higher in AGAs (HR: 5.51, 95% CI: 1.68 to 18.1), and lower in former/current smokers (HR: 0.24, 95% CI: 0.08 to 0.75). The odds of major...