Hengyang Medical School, Graduate Collaborative Training Base of Hunan Cancer Hospital, University of South China, Hengyang, 421001, Hunan, China.
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, 410013, China.
BMC Cancer. 2024 Aug 3;24(1):952. doi: 10.1186/s12885-024-12748-y.
Limited data exists on the efficacy of immune checkpoint inhibitor (ICI) combinations in non-small-cell lung cancer (NSCLC) with uncommon driver alterations in genes such as ERBB2, BRAF, RET, and MET. This study retrospectively assessed ICI-combination therapy outcomes in this molecular subset of NSCLC.
We retrospectively analyzed patients with advanced NSCLC confirmed with driver alterations in genes including ERBB2, BRAF, RET or MET, and received ICI combined with chemotherapy (ICI + chemo) and/or targeted therapy (ICI + chemo/TT) as first-line (1L) or second- or third-line (≥ 2L) treatment at Hunan Cancer Hospital between January 2018 and May 2024.
Of the 181 patients included in the study, 131 patients received 1L-ICI + chemo (ERBB2, n = 64; BRAF, n = 34; RET, n = 23; and MET, n = 10), and 50 patients received ≥ 2L-ICI + chemo/TT (ERBB2, n = 16; BRAF, n = 7; RET, n = 14; MET, n = 13). The full cohort had an overall response rate (ORR) of 45.9% and disease control rate of 84.0%. Among patients who received 1L-ICI + chemo, ORR ranged between 51.6% and 60.0%, with the median progression-free survival (mPFS) and overall survival (mOS) of 8.2 and 21.0 months for those with ERBB2-altered tumors, 10.0 and 15.0 months for BRAF-altered tumors, 12.1 months and OS not reached for RET-altered tumors, and 6.2 and 28.0 months for MET-altered tumors, respectively. Additionally, ORR ranged between 14.3% and 30.8% for ≥ 2L-ICI + chemo/TT; mPFS and mOS were 5.4 and 16.2 months for patients with ERBB2-altered tumors, 2.7 and 5.0 months for BRAF-altered tumors, 6.2 and 14.3 months for RET-altered tumors, and 5.7 and 11.5 months for MET-altered tumors, respectively.
ICI-based combination therapies, regardless of treatment line, were effective in treating patients with advanced NSCLC harboring driver alterations in ERBB2, BRAF, RET, or MET. This suggests their potential as alternative treatment options in this patient population.
在 ERBB2、BRAF、RET 和 MET 等罕见驱动基因改变的非小细胞肺癌（NSCLC）患者中，免疫检查点抑制剂（ICI）联合治疗的疗效数据有限。本研究回顾性评估了这一 NSCLC 分子亚组中 ICI 联合治疗的疗效。
我们回顾性分析了 2018 年 1 月至 2024 年 5 月期间在湖南省肿瘤医院接受含 ICI 的化疗（ICI+化疗）和/或靶向治疗（ICI+化疗/TT）作为一线（1L）或二线或三线（≥2L）治疗的晚期 NSCLC 患者的基因改变，这些患者的基因改变包括 ERBB2、BRAF、RET 或 MET。
在 181 名患者中，131 名患者接受了 1L-ICI+化疗（ERBB2，n=64；BRAF，n=34；RET，n=23；MET，n=10），50 名患者接受了≥2L-ICI+化疗/TT（ERBB2，n=16；BRAF，n=7；RET，n=14；MET，n=13）。全队列的总缓解率（ORR）为 45.9%，疾病控制率为 84.0%。在接受 1L-ICI+化疗的患者中，ORR 范围为 51.6%至 60.0%，ERBB2 改变肿瘤的中位无进展生存期（mPFS）和总生存期（mOS）分别为 8.2 和 21.0 个月，BRAF 改变肿瘤分别为 10.0 和 15.0 个月，RET 改变肿瘤分别为 12.1 个月和未达到 OS，MET 改变肿瘤分别为 6.2 和 28.0 个月。此外，≥2L-ICI+化疗/TT 的 ORR 范围为 14.3%至 30.8%；ERBB2 改变肿瘤的 mPFS 和 mOS 分别为 5.4 和 16.2 个月，BRAF 改变肿瘤分别为 2.7 和 5.0 个月，RET 改变肿瘤分别为 6.2 和 14.3 个月，MET 改变肿瘤分别为 5.7 和 11.5 个月。
基于 ICI 的联合治疗，无论治疗线如何，在治疗 ERBB2、BRAF、RET 或 MET 改变的晚期 NSCLC 患者中均有效。这表明它们可能是该患者人群的替代治疗选择。
