LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
Advanced Analytics, Parexel, Newton, MA.
Clin Lung Cancer. 2024 Nov;25(7):e362-e368. doi: 10.1016/j.cllc.2024.06.005. Epub 2024 Jun 29.
CheckMate 227 (NCT02477826) evaluated first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic nonsmall cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) expression ≥ 1% or < 1% and no EGFR/ALK alterations. However, many patients randomized to chemotherapy received subsequent immunotherapy. Here, overall survival (OS) and relative OS benefit of nivolumab-plus-ipilimumab were adjusted for potential bias introduced by treatment switching.
Treatment-switching adjustment analyses were conducted following the NICE Decision Support Unit Technical Support Document 16, for CheckMate 227 Part 1 OS data from treated patients (database lock, July 2, 2019). Inverse probability of censoring weighting (IPCW) was used in the base-case analysis; other methods were explored as sensitivity analyses.
Of 1166 randomized patients, 391 (PD-L1 ≥ 1%) and 185 (PD-L1 < 1%) patients received nivolumab-plus-ipilimumab; 387 (PD-L1 ≥ 1%) and 183 (PD-L1 < 1%) patients received chemotherapy, with 29.3-month minimum follow-up. Among chemotherapy-treated patients, 169/387 (43.7%; PD-L1 ≥ 1%) and 66/183 (36.1%; PD-L1 < 1%) switched to immunotherapy poststudy. Among treated patients, median OS was 17.4 months with nivolumab-plus-ipilimumab versus 14.9 months with chemotherapy (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.68-0.95) in the PD-L1 ≥ 1% subgroup and 17.1 versus 12.4 months (HR, 0.62; 95% CI, 0.49-0.80) in the PD-L1 < 1% subgroup. After treatment-switching adjustment using IPCW, the HR (95% CI) for OS for nivolumab-plus-ipilimumab versus chemotherapy was reduced to 0.68 (0.56-0.83; PD-L1 ≥ 1%) and 0.53 (0.40-0.69; PD-L1 < 1%). Sensitivity analyses supported the robustness of the results.
Treatment-switching adjustments resulted in a greater estimated relative OS benefit with first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic NSCLC.
CheckMate 227（NCT02477826）评估了一线纳武利尤单抗联合伊匹单抗与化疗在程序性死亡配体 1（PD-L1）表达≥1%或<1%且无 EGFR/ALK 改变的转移性非小细胞肺癌（NSCLC）患者中的疗效。然而，许多接受化疗的随机患者随后接受了免疫治疗。在这里，通过治疗转换引入的潜在偏倚对纳武利尤单抗联合伊匹单抗的总生存期（OS）和相对 OS 获益进行了调整。
根据 NICE 决策支持单位技术支持文件 16，对 CheckMate 227 第 1 部分 OS 数据（数据库锁定，2019 年 7 月 2 日）进行了治疗转换调整分析。采用逆概率 censoring 加权（IPCW）进行基础分析；还探索了其他方法作为敏感性分析。
在 1166 名随机患者中，391 名（PD-L1≥1%）和 185 名（PD-L1<1%）患者接受了纳武利尤单抗联合伊匹单抗治疗；387 名（PD-L1≥1%）和 183 名（PD-L1<1%）患者接受了化疗，随访时间最短为 29.3 个月。在接受化疗的患者中，169/387 名（PD-L1≥1%）和 66/183 名（PD-L1<1%）患者在研究后转为免疫治疗。在治疗患者中，纳武利尤单抗联合伊匹单抗治疗的中位 OS 为 17.4 个月，而化疗为 14.9 个月（HR，0.80；95%CI，0.68-0.95）在 PD-L1≥1%亚组中，PD-L1<1%亚组为 17.1 个月对 12.4 个月（HR，0.62；95%CI，0.49-0.80）。使用 IPCW 进行治疗转换调整后，纳武利尤单抗联合伊匹单抗与化疗的 OS 的 HR（95%CI）降低至 0.68（0.56-0.83；PD-L1≥1%）和 0.53（0.40-0.69；PD-L1<1%）。敏感性分析支持结果的稳健性。
治疗转换调整后，转移性 NSCLC 患者一线纳武利尤单抗联合伊匹单抗与化疗相比，OS 获益估计更大。
