Wang Haowei, Cheng Lei, Chen Jian, Chen Peixin, Tang Zhuoran, Wang Qianyi, Ma Ying, Zhao Chao, Li Xuefei, Jiang Tao, Zhou Fei, Chen Xiaoxia, Zhou Caicun
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Cancer Immunol Immunother. 2025 Feb 1;74(3):89. doi: 10.1007/s00262-024-03937-6.
PD-1 blockade plus chemotherapy has become the first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without oncogenic drivers. Oncogenic-driven advanced NSCLC showed limited response to PD-1 blockade monotherapy or chemotherapy alone. Whether NSCLC patients with oncogenic drivers could benefit from PD-1 blockade plus chemotherapy remains undetermined.
Three hundred twelve NSCLC patients with at least one oncogenic driver alteration received PD-1 plus chemotherapy or each monotherapy were retrospectively identified. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared to evaluate the therapeutic outcomes differences among patients with different oncogenic drivers.
One hundred sixty-two patients received PD-1 blockade plus chemotherapy, 57 received PD-1 blockade monotherapy and 93 received chemotherapy alone were included. Oncogenic driver mutations including KRAS (31.4%), EGFR (28.8%), HER2 (14.7%), BRAF (10.6%), RET (7.4%), and other mutations (7.1%) were identified. Patients with oncogenic drivers who received PD-1 blockade plus chemotherapy had significantly better outcomes compared to those received PD-1 blockade or chemotherapy alone (ORR: 51% vs. 18% vs. 25%, P < 0.001; median PFS: 10.0 [95% CI: 8.9-12.6] vs. 3.7 [95% CI: 2.9-5.1] vs. 5.3 [95% CI: 4.5-6.2] months, P < 0.001; median OS: 26.0 [95% CI: 23.0-30.0] vs. 14.3 [95% CI: 9.6-19.8] vs. 16.1 [95% CI: 11.6-21.9] months, P < 0.001). The superior efficacy was consistently found in separate analyses for patients received first-line and second/third line treatments. Among individual gene alterations, patients with KRAS, EGFR, or BRAF mutations treated with PD-1 blockade plus chemotherapy achieved markedly improved PFS and OS than those received PD-1 blockade or chemotherapy alone. Multivariate Cox regression analysis revealed that PD-1 blockade plus chemotherapy was independently associated with better PFS and OS.
PD-1 blockade plus chemotherapy demonstrated superior efficacy than PD-1 blockade monotherapy or chemotherapy alone in patients with oncogenic-driven advanced NSCLC, particularly in KRAS, EGFR and BRAF subgroups. These findings suggest that PD-1 blockade plus chemotherapy may be considered as an optional treatment option for patients without available targeted therapies.
程序性死亡受体1（PD-1）阻断联合化疗已成为无致癌驱动因素的晚期非小细胞肺癌（NSCLC）患者的一线标准治疗方案。致癌驱动的晚期NSCLC对单独的PD-1阻断单药治疗或化疗反应有限。具有致癌驱动因素的NSCLC患者是否能从PD-1阻断联合化疗中获益仍未确定。
回顾性纳入312例至少有1种致癌驱动因素改变的NSCLC患者，这些患者接受了PD-1联合化疗或每种单药治疗。比较客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS），以评估不同致癌驱动因素患者的治疗结果差异。
纳入162例接受PD-1阻断联合化疗的患者、57例接受PD-1阻断单药治疗的患者和93例接受单纯化疗的患者。鉴定出致癌驱动基因突变包括KRAS（31.4%）、表皮生长因子受体（EGFR，28.8%）、人表皮生长因子受体2（HER2，14.7%）、BRAF（10.6%）、转染重排（RET，7.4%）和其他突变（7.1%）。与接受PD-1阻断单药治疗或单纯化疗的致癌驱动因素患者相比，接受PD-1阻断联合化疗的患者结局显著更好（ORR：51% 对18% 对25%，P<0.001；中位PFS：10.0[95%置信区间（CI）：8.9-12.6]个月对3.7[95%CI：2.9-5.1]个月对5.3[95%CI：4.5-6.2]个月，P<0.001；中位OS：26.0[95%CI：23.0-30.0]个月对14.3[95%CI：9.6-19.8]个月对16.1[95%CI：11.6-21.9]个月，P<0.001）。在接受一线和二线/三线治疗的患者的单独分析中一致发现了这种卓越疗效。在个体基因改变中，接受PD-1阻断联合化疗治疗的KRAS、EGFR或BRAF突变患者的PFS和OS比接受PD-1阻断单药治疗或单纯化疗的患者显著改善。多因素Cox回归分析显示，PD-1阻断联合化疗与更好的PFS和OS独立相关。
在致癌驱动的晚期NSCLC患者中，PD-1阻断联合化疗显示出比PD-1阻断单药治疗或单纯化疗更卓越的疗效，尤其是在KRAS、EGFR和BRAF亚组中。这些发现表明，对于没有可用靶向治疗的患者，PD-1阻断联合化疗可被视为一种可选的治疗方案。
