纳武利尤单抗联合伊匹单抗对比其他晚期非小细胞肺癌一线治疗的长期疗效和安全性的系统文献评价和网络荟萃分析。

Long-term comparative efficacy and safety of nivolumab plus ipilimumab relative to other first-line therapies for advanced non-small-cell lung cancer: A systematic literature review and network meta-analysis.

机构信息

Queensland University of Technology, Princess Alexandra Hospital, Brisbane, Australia.

Broadstreet HEOR, 201-343 Railway St, Vancouver BC, Canada.

出版信息

Lung Cancer. 2023 Mar;177:11-20. doi: 10.1016/j.lungcan.2023.01.006. Epub 2023 Jan 11.

DOI:10.1016/j.lungcan.2023.01.006

PMID:36669321

Abstract

OBJECTIVES

To quantify the long-term comparative efficacy and safety of nivolumab in combination with ipilimumab (NIVO + IPI) relative to other immunotherapy (IO)-based regimens and chemotherapy in patients with first-line advanced non-small cell lung cancer (aNSCLC).

METHODS

Phase 3 randomized controlled-trials (RCTs) with minimum 3-year follow-up evaluating IO-based regimens approved for first-line aNSCLC were identified via systematic literature review. Analytic populations were defined by levels of PD-L1 expression and histology. Due to presence of proportional hazards violations, time-varying hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were estimated via Bayesian fractional polynomial network meta-analysis. For safety endpoints, odds ratios (ORs) were estimated using indirect treatment comparisons (ITCs).

RESULTS

CheckMate 227, KEYNOTE-189, KEYNOTE-407, KEYNOTE-024, KEYNOTE-042, and IMpower150 were included in the base case analysis. For OS and PFS, HRs of NIVO + IPI relative to other IO-based regimens trended downward over time across analytic populations. The 36-month OS HRs of NIVO + IPI versus comparators were: 0.69 (95 % credible interval: 0.47, 1.00) versus pembrolizumab + chemotherapy and 0.65 (0.45, 0.93) versus atezolizumab + bevacizumab + chemotherapy in the non-squamous and PD-L1 all-comers population; 0.73 (0.53, 1.02) versus pembrolizumab + chemotherapy in the squamous and PD-L1 all-comers population; and 1.05 (0.83, 1.32) versus pembrolizumab in the mixed histology and PD-L1 ≥ 50 % population. For PFS, 36-month HR point estimates ranged from 0.46 to 0.85 (only statistically significant versus pembrolizumab + chemotherapy in the squamous population; 0.46 [0.31, 0.69]). Adverse events (AEs) leading to discontinuation were not statistically significantly different between NIVO + IPI and pembrolizumab + chemotherapy, nor between NIVO + IPI and pembrolizumab monotherapy, although treatment-related grade ≥ 3 AEs were higher with NIVO + IPI than pembrolizumab monotherapy (OR = 2.21 [1.30, 3.75]).

CONCLUSIONS

This study indicates trends towards long-term benefit with NIVO + IPI compared with other IO-based combinations, with manageable toxicities.

摘要

目的

通过贝叶斯分数多项式网络荟萃分析，定量评估纳武利尤单抗联合伊匹单抗（NIVO+IPI）与其他免疫治疗（IO）方案和化疗一线治疗晚期非小细胞肺癌（aNSCLC）的长期比较疗效和安全性。

方法

通过系统文献回顾，确定了具有至少 3 年随访的评估一线 aNSCLC 中 IO 方案的 III 期随机对照试验（RCT）。分析人群根据 PD-L1 表达和组织学水平定义。由于存在比例风险违反，通过贝叶斯分数多项式网络荟萃分析估计总生存期（OS）和无进展生存期（PFS）的时变风险比（HR）。对于安全性终点，使用间接治疗比较（ITC）估计比值比（OR）。

结果

在基础案例分析中，纳入了 CheckMate 227、KEYNOTE-189、KEYNOTE-407、KEYNOTE-024、KEYNOTE-042 和 IMpower150 试验。对于 OS 和 PFS，NIVO+IPI 与其他 IO 方案的 HR 随时间呈下降趋势。NIVO+IPI 与对照组相比的 36 个月 OS HR 为：非鳞状细胞和 PD-L1 所有患者人群中，0.69（95%可信区间：0.47，1.00）对比帕博利珠单抗+化疗，0.65（0.45，0.93）对比阿替利珠单抗+贝伐珠单抗+化疗；鳞状细胞和 PD-L1 所有患者人群中，0.73（0.53，1.02）对比帕博利珠单抗+化疗；混合组织学和 PD-L1≥50%人群中，1.05（0.83，1.32）对比帕博利珠单抗。对于 PFS，36 个月 HR 点估计值范围为 0.46 至 0.85（仅在鳞状细胞人群中与帕博利珠单抗+化疗有统计学意义；0.46 [0.31，0.69]）。NIVO+IPI 与帕博利珠单抗+化疗之间，以及 NIVO+IPI 与帕博利珠单抗单药治疗之间，导致停药的不良事件（AE）无统计学显著差异，但与帕博利珠单抗单药治疗相比，NIVO+IPI 治疗相关的≥3 级 AE 更高（OR=2.21 [1.30，3.75]）。