National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
J Clin Oncol. 2024 Dec;42(34):4029-4039. doi: 10.1200/JCO.23.02747. Epub 2024 Aug 22.
Epidermal growth factor receptor () tyrosine kinase inhibitors (TKIs) are standard first-line therapy for -mutant, metastatic non-small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum-based chemotherapy with or without pembrolizumab for TKI-resistant, -mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837).
Adults with pathologically confirmed stage IV nonsquamous NSCLC, documented or mutation, and progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus four cycles of pemetrexed and carboplatin or cisplatin once every 3 weeks and then maintenance pemetrexed. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Final PFS testing was completed at the second interim analysis (IA2; data cutoff, December 3, 2021); OS was tested at final analysis (FA; data cutoff, January 17, 2023). Efficacy boundaries were one-sided = .0117 for PFS and OS.
Four hundred ninety-two patients were randomly assigned to pembrolizumab plus chemotherapy (n = 245) or placebo plus chemotherapy (n = 247). At IA2, the median PFS was 5.6 months for pembrolizumab plus chemotherapy versus 5.5 months for placebo plus chemotherapy (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.97]; = .0122). At FA, the median OS was 15.9 versus 14.7 months, respectively (HR, 0.84 [95% CI, 0.69 to 1.02]; = .0362). Grade ≥3 treatment-related adverse events occurred in 43.7% of pembrolizumab plus chemotherapy recipients versus 38.6% of placebo plus chemotherapy recipients.
Addition of pembrolizumab to chemotherapy in patients with TKI-resistant, -mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy in KEYNOTE-789.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）是 - 突变型转移性非小细胞肺癌（NSCLC）的标准一线治疗药物；然而，大多数患者会出现疾病进展。我们报告了 KEYNOTE-789 随机、双盲、III 期研究的结果，该研究评估了培美曲塞和铂类化疗联合或不联合 pembrolizumab 用于 TKI 耐药、 - 突变、转移性非鳞状 NSCLC（ClinicalTrials.gov 标识符：NCT03515837）。
经病理证实为 IV 期非鳞状 NSCLC、有记录的 或 突变以及 EGFR-TKI 治疗后进展的成年患者按 1:1 随机分配，接受 35 个周期的 pembrolizumab 200mg 或安慰剂，每 3 周一次，联合培美曲塞和卡铂或顺铂，每 3 周一次，然后进行培美曲塞维持治疗。主要终点为无进展生存期（PFS）和总生存期（OS）。最终 PFS 测试在第二次中期分析（IA2；数据截止日期，2021 年 12 月 3 日）完成；OS 在最终分析（FA；数据截止日期，2023 年 1 月 17 日）进行测试。疗效边界为单侧 PFS 和 OS 的 =.0117。
492 名患者被随机分配至 pembrolizumab 联合化疗组（n = 245）或安慰剂联合化疗组（n = 247）。在 IA2 时，pembrolizumab 联合化疗的中位 PFS 为 5.6 个月，安慰剂联合化疗的中位 PFS 为 5.5 个月（HR，0.80 [95%CI，0.65 至 0.97]；=.0122）。在 FA 时，中位 OS 分别为 15.9 个月和 14.7 个月（HR，0.84 [95%CI，0.69 至 1.02]；=.0362）。pembrolizumab 联合化疗组 43.7%的患者和安慰剂联合化疗组 38.6%的患者发生≥3 级治疗相关不良事件。
在 KEYNOTE-789 中，与安慰剂联合化疗相比，pembrolizumab 联合化疗并未显著延长 TKI 耐药、 - 突变、转移性非鳞状 NSCLC 患者的 PFS 或 OS。
