免疫检查点抑制剂联合化疗与单纯化疗作为广泛期小细胞肺癌一线治疗。
Immune-checkpoint inhibitors plus chemotherapy versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer.
机构信息
Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Department of Radiation Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
出版信息
J Immunother Cancer. 2020 Sep;8(2). doi: 10.1136/jitc-2020-001300.
We performed a meta-analysis to comprehensively investigate the efficacy and safety of immune-checkpoint inhibitors (ICIs) plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and ≥grade 3 adverse events (AEs). A total of six studies involving 2905 patients were identified, including 469 patients receiving program death ligand 1 (PD-L1) inhibitor plus chemotherapy, 308 receiving PD-1 inhibitors plus chemotherapy, 563 receiving CTLA-4 inhibitors plus chemotherapy, 268 receiving PD-L1/CTLA-4 inhibitors plus chemotherapy, and 1297 receiving chemotherapy alone. 10.8% (283/2615) patients had baseline brain metastases (BMs). Notably, ICIs plus chemotherapy was associated with significantly improved OS (HR, 0.82; 95% CI, 0.75 to 0.89). Subgroup analyses revealed that PD-1 inhibitors (HR, 0.77; 95% CI, 0.64 to 0.92) and PD-L1 inhibitors (HR, 0.73; 95% CI, 0.63 to 0.85) plus chemotherapy yielded a statistically significant improvement in OS while CTLA-4 inhibitors did not (HR, 0.92; 95% CI, 0.81 to 1.06). In patients with baseline BMs, ICIs plus chemotherapy showed no survival benefits over chemotherapy alone (HR, 1.23; 95% CI, 0.92 to 1.64). ICIs plus chemotherapy also significantly prolonged PFS (HR, 0.81; 95% CI, 0.75 to 0.87) while the pooled ORRs were comparable between ICIs plus chemotherapy and chemotherapy alone (RR, 1.04; 95% CI, 0.99 to 1.10). Patients treated with CTLA-4 inhibitors (relative risk (RR), 1.12; 95% CI, 0.99 to 1.28) experienced more≥grade 3 AEs than those treated with PD-1/PD-L1 inhibitors (RR, 1.03; 95% CI, 0.96 to 1.11). The addition of PD-1/PD-L1 inhibitors to chemotherapy resulted in significant improvements in both PFS and OS for patients with treatment-naïve ES-SCLC, not at the cost of increased AEs.
我们进行了一项荟萃分析，全面研究了免疫检查点抑制剂（ICI）联合化疗在广泛期小细胞肺癌（ES-SCLC）患者中的疗效和安全性。主要结局是总生存期（OS）。次要结局包括无进展生存期（PFS）、客观缓解率（ORR）和≥3 级不良事件（AE）。共纳入了 6 项研究，涉及 2905 例患者，其中 469 例接受了程序性死亡配体 1（PD-L1）抑制剂联合化疗，308 例接受了 PD-1 抑制剂联合化疗，563 例接受了 CTLA-4 抑制剂联合化疗，268 例接受了 PD-L1/CTLA-4 抑制剂联合化疗，1297 例接受了单纯化疗。2615 例患者中有 10.8%（283 例）基线时有脑转移（BM）。值得注意的是，ICI 联合化疗显著改善了 OS（HR，0.82；95%CI，0.75 至 0.89）。亚组分析显示，PD-1 抑制剂（HR，0.77；95%CI，0.64 至 0.92）和 PD-L1 抑制剂（HR，0.73；95%CI，0.63 至 0.85）联合化疗可显著改善 OS，而 CTLA-4 抑制剂则不能（HR，0.92；95%CI，0.81 至 1.06）。在基线有 BM 的患者中，ICI 联合化疗与单纯化疗相比并未带来生存获益（HR，1.23；95%CI，0.92 至 1.64）。ICI 联合化疗还显著延长了 PFS（HR，0.81；95%CI，0.75 至 0.87），而 ICI 联合化疗与单纯化疗的 ORR 相当（RR，1.04；95%CI，0.99 至 1.10）。与 PD-1/PD-L1 抑制剂相比，接受 CTLA-4 抑制剂治疗的患者（RR，1.12；95%CI，0.99 至 1.28）发生≥3 级 AE 的风险更高（RR，1.03；95%CI，0.96 至 1.11）。在未经治疗的 ES-SCLC 患者中，PD-1/PD-L1 抑制剂联合化疗可显著改善 PFS 和 OS，且不会增加 AE。
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