Docetaxel +/− ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/− ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/− ramucirumabn=381; platinum/taxane-based regimensn=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/− ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/− ramucirumab, the top mutated cancer genes included TP53(n=167), KRAS(n=127), EGFR(n=65), STK11(n=32), ERBB2 (HER2)(n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20–14.80 m versus 8.40 m, 95% Cl: 7.12–9.68 m, LogRankP=0.019) than docetaxel +/− ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/− ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/− ramucirumab in this patient population.
对于铂类双药化疗及免疫检查点抑制剂（ICIs）治疗后进展的转移性非小细胞肺癌（NSCLC）患者，多西他赛联合或不联合雷莫西尤单抗仍是标准治疗方案。本研究旨在探讨癌症基因突变状态是否与多西他赛联合或不联合雷莫西尤单抗的临床获益相关，同时评估铂类/紫杉烷类方案是否能为该患者群体带来更优的临床获益。共纳入454例患者进行分析（多西他赛联合或不联合雷莫西尤单抗组381例；铂类/紫杉烷类方案组73例）。研究比较了不同癌症基因突变亚组间，以及接受多西他赛联合或不联合雷莫西尤单抗与铂类/紫杉烷类方案治疗患者间的无进展生存期（PFS）和总生存期（OS）。在多西他赛联合或不联合雷莫西尤单抗治疗的患者中，高频突变癌症基因包括TP53（167例）、KRAS（127例）、EGFR（65例）、STK11（32例）、ERBB2（HER2）（26例）等。这些癌症基因突变及PD-L1表达均未显示与PFS或OS存在相关性。铂类/紫杉烷类方案组的中位生存期（mQS）显著长于多西他赛联合或不联合雷莫西尤单抗组（13.00个月，95% CI：11.20-14.80个月 vs 8.40个月，95% CI：7.12-9.68个月，LogRank P=0.019）。两组在年龄、组织学类型、体能状态等关键预后因素方面无显著差异。结论表明，对于铂类双药化疗及ICIs治疗后进展的转移性NSCLC患者，多西他赛联合或不联合雷莫西尤单抗的临床获益与癌症基因突变状态无关。在该患者群体中，铂类/紫杉烷类方案可能较多西他赛联合或不联合雷莫西尤单抗提供更优的临床获益。
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