Department of Oncology, Johns Hopkins School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
Clin Lung Cancer. 2022 Nov;23(7):620-629. doi: 10.1016/j.cllc.2022.08.002. Epub 2022 Aug 8.
Consolidation durvalumab immunotherapy following definitive chemoradiation (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) improves overall survival. As therapeutic options for patients with KRAS-driven disease evolve, more understanding regarding genomic determinants of response and patterns of progression for durvalumab consolidation is needed to optimize outcomes.
We conducted a single-institutional retrospective analysis of real-world patients with locally advanced, unresectable NSCLC who completed CRT and received durvalumab consolidation. Kaplan-Meier analyses compared progression-free survival (PFS) and overall survival (OS) from start of durvalumab consolidation between patients with KRAS-mutated and non-mutated tumors. Fisher's exact test was used to compare rates of intrathoracic or extrathoracic progression.
Of 74 response-evaluable patients, 39 had clinical genomic profiling performed. 18 patients had tumors with KRAS mutations, 7 patients had tumors with non-KRAS actionable alterations (EGFR, ALK, ERBB2, BRAF, MET, RET, or ROS1), and 14 patients had tumors without actionable alterations. Median PFS for the overall cohort was 16.1 months. PFS for patients with KRAS-mutated NSCLC was 12.6 months versus 12.7 months for patients with non-actionable tumors (P= 0.77, log-rank). Fisher's exact test revealed a statistically significantly higher rate of extrathoracic progression versus intrathoracic-only progression for patients with KRAS-driven disease compared to patients with non-actionable tumors (P= 0.015).
Patients with KRAS-mutated NSCLC derived similar benefit from durvalumab as patients with non-actionable tumors. A higher rate of extrathoracic progression was also observed among the patients with KRAS-mutated NSCLC compared to patients with non-actionable tumors. This highlights the potential unmet needs for novel systemic therapies and surveillance methods for KRAS-mutated stage III NSCLC.
对于不可切除的 III 期非小细胞肺癌（NSCLC）患者，在放化疗后进行度伐利尤单抗巩固免疫治疗可改善总生存期。随着针对 KRAS 驱动型疾病的治疗选择的发展，为了优化结果，需要更多地了解度伐利尤单抗巩固治疗的反应的基因组决定因素和进展模式。
我们对完成放化疗并接受度伐利尤单抗巩固治疗的局部晚期、不可切除 NSCLC 患者进行了单机构回顾性分析。Kaplan-Meier 分析比较了 KRAS 突变和非突变肿瘤患者从度伐利尤单抗开始巩固治疗后的无进展生存期（PFS）和总生存期（OS）。Fisher 确切检验用于比较胸内或胸外进展的发生率。
在 74 例可评价疗效的患者中，39 例进行了临床基因组分析。18 例患者肿瘤存在 KRAS 突变，7 例患者肿瘤存在非 KRAS 可治疗性改变（EGFR、ALK、ERBB2、BRAF、MET、RET 或 ROS1），14 例患者肿瘤不存在可治疗性改变。总队列的中位 PFS 为 16.1 个月。KRAS 突变 NSCLC 患者的 PFS 为 12.6 个月，无治疗靶点肿瘤患者的 PFS 为 12.7 个月（P=0.77，对数秩检验）。Fisher 确切检验显示，与无治疗靶点肿瘤患者相比，KRAS 驱动型疾病患者的胸外进展率显著高于胸内进展率（P=0.015）。
KRAS 突变 NSCLC 患者从度伐利尤单抗治疗中获益与无治疗靶点肿瘤患者相似。与无治疗靶点肿瘤患者相比，KRAS 突变 NSCLC 患者也观察到更高的胸外进展率。这凸显了针对 III 期 KRAS 突变 NSCLC 患者的新型系统治疗和监测方法的潜在未满足需求。
