CheckMate 227 第一部分评估转移性非小细胞肺癌一线 Nivolumab 加 Ipilimumab 与化疗的总生存期治疗转换调整试验

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-06-29 DOI:10.1016/j.cllc.2024.06.005

Martin Reck , Tuli De , Luis Paz-Ares , Mark Edmondson-Jones , Yong Yuan , Georgia Yates , Roberto Zoffoli , Mohammad Ashraf Chaudhary , Adam Lee , Nebibe Varol , John R. Penrod

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引用次数: 0

摘要

CheckMate 227 (NCT02477826)评估了程序性死亡配体1（PD-L1）表达≥1%或<1%且无/改变的转移性非小细胞肺癌（NSCLC）患者的一线nivolumab-plus-ipilimumab与化疗的对比。然而，许多随机接受化疗的患者随后又接受了免疫疗法。在此，对nivolumab-plus-ipilimumab的总生存期（OS）和相对OS获益进行了调整，以消除治疗转换带来的潜在偏差。治疗转换调整分析是根据NICE决策支持部门技术支持文件16，针对CheckMate 227第1部分治疗患者的OS数据（数据库锁定时间为2019年7月2日）进行的。在基础案例分析中使用了逆概率删减加权法（IPCW）；在敏感性分析中探讨了其他方法。在1166例随机患者中，391例（PD-L1≥1%）和185例（PD-L1<1%）患者接受了nivolumab-plus-ipilimumab治疗；387例（PD-L1≥1%）和183例（PD-L1<1%）患者接受了化疗，随访时间最短为29.3个月。化疗患者中，169/387（43.7%；PD-L1≥1%）和66/183（36.1%；PD-L1<1%）人在研究后转为免疫疗法。在接受治疗的患者中，PD-L1≥1%亚组中，nivolumab加伊匹单抗的中位OS为17.4个月，化疗为14.9个月（危险比[HR]，0.80；95%置信区间[CI]，0.68-0.95）；PD-L1<1%亚组中，中位OS为17.1个月，化疗为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，nivolumab加伊匹单抗与化疗相比的OS HR（95%CI）分别降至0.68（0.56-0.83；PD-L1≥1%）和0.53（0.40-0.69；PD-L1<1%）。敏感性分析证实了结果的稳健性。在转移性NSCLC患者中，治疗转换调整使一线nivolumab-plus-ipilimumab相对于化疗的估计相对OS获益更大。

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Treatment-Switching Adjustment of Overall Survival in CheckMate 227 Part 1 Evaluating First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy for Metastatic Nonsmall Cell Lung Cancer

Objectives

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.

Materials and methods

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.

Results

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.

Conclusion

Treatment-switching adjustments resulted in a greater estimated relative OS benefit with first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic NSCLC.

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567