Karmanos Cancer Institute, Detroit, MI.
Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
J Clin Oncol. 2020 May 10;38(14):1505-1517. doi: 10.1200/JCO.19.03136. Epub 2020 Mar 9.
PURPOSE: In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680). METHODS: Patients were randomly assigned (2:1) to receive pemetrexed and platinum plus pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for 4 cycles, then pemetrexed maintenance plus pembrolizumab or placebo for up to a total of 35 cycles. Eligible patients with disease progression in the placebo-combination group could cross over to pembrolizumab monotherapy. Response was assessed per RECIST (version 1.1) by central review. No alpha was assigned to this updated analysis. RESULTS: As of September 21, 2018 (median follow-up, 23.1 months), the updated median (95% CI) OS was 22.0 (19.5 to 25.2) months in the pembrolizumab-combination group versus 10.7 (8.7 to 13.6) months in the placebo-combination group (hazard ratio [HR], 0.56; 95% CI, 0.45 to 0.70]). Median (95% CI) PFS was 9.0 (8.1 to 9.9) months and 4.9 (4.7 to 5.5) months, respectively (HR, 0.48; 95% CI, 0.40 to 0.58). Median (95% CI) time from randomization to objective tumor progression on next-line treatment or death from any cause, whichever occurred first (progression-free-survival-2; PFS-2) was 17.0 (15.1 to 19.4) months and 9.0 (7.6 to 10.4) months, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). OS and PFS benefits with pembrolizumab were observed regardless of PD-L1 expression or presence of liver/brain metastases. Incidence of grade 3-5 adverse events was similar in the pembrolizumab-combination (71.9%) and placebo-combination (66.8%) groups. CONCLUSION: First-line pembrolizumab plus pemetrexed-platinum continued to demonstrate substantially improved OS and PFS in metastatic nonsquamous NSCLC, regardless of PD-L1 expression or liver/brain metastases, with manageable safety and tolerability.
目的：在 KEYNOTE-189 中，一线帕博利珠单抗联合培美曲塞-铂类对比安慰剂联合培美曲塞-铂类在转移性非鳞状非小细胞肺癌（NSCLC）患者中显著改善了总生存期（OS）和无进展生存期（PFS），无论肿瘤程序性死亡配体 1（PD-L1）表达如何。我们报告了 KEYNOTE-189 的更新分析（ClinicalTrials.gov：NCT02578680）。
方法：患者按 2:1 的比例随机分配（n = 410）接受培美曲塞和铂类联合帕博利珠单抗（n = 410）或安慰剂（n = 206）每 3 周治疗 4 个周期，然后接受培美曲塞维持治疗联合帕博利珠单抗或安慰剂治疗，最多 35 个周期。安慰剂联合组中疾病进展的符合条件患者可交叉至帕博利珠单抗单药治疗。采用中心审查评估 RECIST（版本 1.1）标准的应答情况。本次更新分析未分配 alpha 值。
结果：截至 2018 年 9 月 21 日（中位随访时间，23.1 个月），更新后的中位（95%CI）OS 为 22.0（19.5 至 25.2）个月，在帕博利珠单抗联合组与安慰剂联合组分别为 10.7（8.7 至 13.6）个月（风险比 [HR]，0.56；95%CI，0.45 至 0.70）。中位（95%CI）PFS 分别为 9.0（8.1 至 9.9）个月和 4.9（4.7 至 5.5）个月（HR，0.48；95%CI，0.40 至 0.58）。从随机分组到下一线治疗的客观肿瘤进展或任何原因导致的死亡（无进展生存期-2；PFS-2）的中位（95%CI）时间分别为 17.0（15.1 至 19.4）个月和 9.0（7.6 至 10.4）个月（HR，0.49；95%CI，0.40 至 0.59）。无论 PD-L1 表达或肝/脑转移情况如何，帕博利珠单抗的 OS 和 PFS 获益均观察到。帕博利珠单抗联合组（71.9%）和安慰剂联合组（66.8%）的 3-5 级不良事件发生率相似。
结论：一线帕博利珠单抗联合培美曲塞-铂类在转移性非鳞状 NSCLC 中继续表现出显著的 OS 和 PFS 改善，无论 PD-L1 表达或肝/脑转移情况如何，且安全性和耐受性可管理。
N Engl J Med. 2018-4-16
Biomedicines. 2025-8-12
MedComm (2020). 2025-8-10
IEEE J Solid-State Circuits. 2024-11
Zotero 插件