Pembrolizumab联合Olaparib与Pembrolizumab联合培美曲塞作为转移性非鳞状非小细胞肺癌维持疗法的3期KEYLYNK-006研究。

IF 21 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology Pub Date : 2025-02-01 DOI:10.1016/j.jtho.2024.10.026

Jhanelle E. Gray MD , Michael Schenker MD, PhD , Mehmet Ali Nahit Şendur MD , Viktoriya Leonova MD , Dariusz Kowalski MD, PhD , Terufumi Kato MD , Rashida Orlova MD , James Chih-Hsin Yang MD, PhD , Adrian Langleben MD , Arnold Pilz MD , Andrei Ungureanu MD , Milena Perez Mak MD , Flavia De Angelis MD , Himani Aggarwal PhD , Zachary Zimmer PhD , Bin Zhao MD, PhD , Mark Shamoun MD , Tae Min Kim MD, PhD

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引用次数: 0

摘要

背景：包括奥拉帕利在内的聚（ADP-核糖）抑制剂会上调程序性细胞死亡配体1（PD-L1），这可能会提高抗PD-(L)1疗法的疗效：在 KEYLYNK-006 3 期试验（NCT03976323）中，符合条件的既往未接受过治疗的转移性非鳞状 NSCLC 患者，如果没有可靶向的基因改变，且在接受 4 个周期的诱导治疗后出现完全应答 (CR)、部分应答 (PR) 或疾病稳定 (SD)，则随机分为 1：奥拉帕利（olaparib）300 毫克，口服，每天两次，或培美曲塞 Q3W，均与≤31 个周期的 pembrolizumab Q3W 同时进行。双重主要终点是无进展生存期（PFS）和总生存期（OS）。无进展生存期在中期分析2（IA2；即最终无进展生存期分析）时进行检测，OS在最终分析（FA）时进行检测：在1003名接受诱导治疗的患者中，672人（67.0%）随机接受了pembrolizumab联合奥拉帕利（337人）或pembrolizumab联合培美曲塞（335人）的意向治疗。FA的中位随访时间为39.9个月（28.1-51.5个月）。在IA2，奥拉帕利与培美曲塞组的中位（95% CI）PFS分别为7.1（5.6-8.7）个月和8.3（6.9-11.5）个月（HR，1.12；95% CI，0.92-1.36；P=0.87）。在FA，中位（95% CI）OS为20.7（18.0-24.8）个月对23.0（19.0-26.4）个月（HR，1.04；95% CI，0.87-1.25；P=0.6649）。3-5级维持治疗相关AE发生率为26.1%对30.1%：Pembrolizumab联合奥拉帕利维持治疗与Pembrolizumab联合培美曲塞相比，并不能改善既往未经治疗的无靶向基因改变的转移性非鳞状NSCLC患者的PFS或OS。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The Phase 3 KEYLYNK-006 Study of Pembrolizumab Plus Olaparib Versus Pembrolizumab Plus Pemetrexed as Maintenance Therapy for Metastatic Nonsquamous NSCLC

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The Phase 3 KEYLYNK-006 Study of Pembrolizumab Plus Olaparib Versus Pembrolizumab Plus Pemetrexed as Maintenance Therapy for Metastatic Nonsquamous NSCLC

Introduction

Poly (adenosine diphosphate–ribose) inhibitors, including olaparib, upregulate programmed cell death ligand 1, which may increase the efficacy of anti–programmed cell death protein 1 and anti–programmed cell death ligand 1 therapies.

Methods

In the phase 3 KEYLYNK-006 trial (NCT03976323), eligible adults with previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations who had complete response, partial response, or stable disease after induction therapy with four cycles of pembrolizumab 200 mg every three weeks, pemetrexed 500 mg/m², and carboplatin area under the concentration-time curve 5 mg/mL/min or cisplatin 75 mg/m² were randomized in a one-to-one ratio to olaparib 300 mg orally twice daily or pemetrexed every three weeks, both given with up to 31 cycles of pembrolizumab every three weeks. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). Progression-free survival was tested at interim analysis 2 (i.e., final PFS analysis) and OS at final analysis (FA).

Results

Of 1003 patients who received induction therapy, 672 (67.0%) were randomized to pembrolizumab plus olaparib (n = 337) or pembrolizumab plus pemetrexed (n = 335) in the intention-to-treat population. Median follow-up at FA was 39.9 (range: 28.1–51.5) months. At interim analysis 2, the median (95% confidence interval [CI]) PFS was 7.1 (5.6–8.7) months versus 8.3 (6.9–11.5) months in the olaparib versus pemetrexed groups (hazard ratio = 1.12, 95% CI: 0.92–1.36, p = 0.87). At FA, the median (95% CI) OS was 20.7 (18.0–24.8) months versus 23.0 (19.0–26.4) months (hazard ratio = 1.04, 95% CI: 0.87–1.25, p = 0.6649). Grade 3 to 5 maintenance treatment-related adverse events occurred in 26.1% versus 30.1% of patients, respectively.

Conclusion

Pembrolizumab plus maintenance olaparib did not improve PFS or OS versus pembrolizumab plus pemetrexed in previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations.

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来源期刊

Journal of Thoracic Oncology 医学-呼吸系统

CiteScore

36.00

自引率

3.90%

发文量

1406

审稿时长

13 days

期刊介绍： Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer,is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies.The readship includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.