■Kirsten大鼠肉瘤同源物(KRAS)突变是非小细胞肺癌(NSCLC)的关键驱动因素之一,FDA批准的KRAS-G12C突变的特异性抑制剂可用于临床。然而,某些KRAS突变亚型的抑制剂仍然不可用,特别是罕见的KRAS突变,包括G13C,G13D,和Q61H。在这项研究中,我们回顾性调查了具有罕见KRAS突变的NSCLC患者的结局,以确定他们是否可以从免疫检查点抑制剂(ICIs)中获益.
■我们的回顾性研究涉及240例KRAS突变的晚期NSCLC患者,他于2018年7月至2021年7月就诊于上海胸科医院。记录完整的临床和病理数据,并采用无进展生存期(PFS)和总生存期(OS)作为主要终点。
■中位随访时间为36.5个月(范围,30.8-42.1个月),中位OS为9.7个月(范围,7.6-11.8个月)。在接受评估的240名患者中,130例(54.2%)接受化疗,110例(45.8%)接受基于ICI的治疗。在接受化疗的患者中,罕见KRAS突变患者的生存结局较差(中位PFS,3.4vs.4.1个月,P=0.047;OS中位数,5.2vs.7.1个月,P=0.02)比常规KRAS突变患者高。免疫治疗后,罕见KRAS突变患者的PFS和OS延长(中位PFS7.3vs.3.4个月,P<0.001;中位OS,13.3vs.5.2个月,P<0.001),与常规KRAS突变患者相比无显着差异,其中一部分在免疫治疗前可获得程序性死亡配体1(PD-L1)表达数据(n=72),肿瘤细胞PD-L1阳性率较高(≥50%)的患者PFS和OS升高.
■尽管与其他非小细胞肺癌患者相比存在潜在的生存劣势,罕见的KRAS突变患者(G12A除外,C,D,V)可以从基于ICI的治疗中特别受益,生存结果与PD-L1表达相关。
UNASSIGNED: Kirsten rat sarcoma homolog (KRAS) mutations are one of the key drivers in non-small cell lung cancer (NSCLC) and FDA-approved specific inhibitors of KRAS-G12C mutation are available clinically. However, inhibitors of certain KRAS mutation subtypes remain unavailable, especially rare KRAS mutations including G13C, G13D, and Q61H. In this study, we retrospectively investigated the outcomes of NSCLC patients with rare KRAS-mutation to determine if they may benefit from immune checkpoint inhibitors (ICIs).
UNASSIGNED: Our retrospective study involved 240 advanced NSCLC patients with KRAS mutations, who visited Shanghai Chest Hospital from July 2018 to July 2021. Complete clinical and pathological data were recorded and progression-free survival (PFS) and overall survival (OS) were adopted as primary endpoints.
UNASSIGNED: The median follow-up time was 36.5 months (range, 30.8-42.1 months) and the median OS was 9.7 months (range, 7.6-11.8 months). Of the 240 patients evaluated, 130 (54.2%) received chemotherapy and 110 (45.8%) received ICI-based treatment. Among the patients who received chemotherapy, patients with rare KRAS-mutations presented worse survival outcomes (median PFS, 3.4 vs. 4.1 months, P=0.047; median OS, 5.2 vs. 7.1 months, P=0.02) than conventional KRAS-mutant patients. PFS and OS of rare KRAS-mutation patients were prolonged after immunotherapy (median PFS 7.3 vs. 3.4 months, P<0.001; median OS, 13.3 vs. 5.2 months, P<0.001) and had no significant difference compared with conventional KRAS-mutant patients, in part of them whose programmed death-ligand 1 (PD-L1) expression data before immunotherapy were available (n=72), patients with a higher rate of PD-L1 positive tumor cells (≥50%) presented elevated PFS and OS.
UNASSIGNED: Despite having potential survival disadvantage compared with other NSCLC patients, rare KRAS-mutant patients (other than G12A, C, D, V) could benefit specifically from ICI-based therapy and survival outcomes are correlated with PD-L1 expression.