Background

In the phase 3 KEYNOTE-061 study (cutoff: 10/26/2017), pembrolizumab did not significantly prolong OS vs paclitaxel as second-line (2L) therapy in PD-L1 combined positive score (CPS) ≥ 1 gastric/GEJ cancer. We present results in CPS ≥ 1, ≥ 5, and ≥ 10 populations after two additional years of follow-up (cutoff: 10/07/2019).

Methods

Patients were randomly allocated 1:1 to pembrolizumab 200 mg Q3W for ≤ 35 cycles or standard-dose paclitaxel. Primary endpoints: OS and PFS (CPS ≥ 1 population). HRs were calculated using stratified Cox proportional hazards models.

Results

366/395 patients (92.7%) with CPS ≥ 1 died. Pembrolizumab demonstrated a trend toward improved OS vs paclitaxel in the CPS ≥ 1 population (HR, 0.81); 24-month OS rates: 19.9% vs 8.5%. Pembrolizumab incrementally increased the OS benefit with PD-L1 enrichment (CPS ≥ 5: HR, 0.72, 24-month rate, 24.2% vs 8.8%; CPS ≥ 10: 0.69, 24-month rate, 32.1% vs 10.9%). There was no difference in median PFS among treatment groups (CPS ≥ 1: HR, 1.25; CPS ≥ 5: 0.98; CPS ≥ 10: 0.79). ORR (pembrolizumab vs paclitaxel) was 16.3% vs 13.6% (CPS ≥ 1), 20.0% vs 14.3% (CPS ≥ 5), and 24.5% vs 9.1% (CPS ≥ 10); median DOR was 19.1 months vs 5.2, 32.7 vs 4.8, and NR vs 6.9, respectively. Fewer treatment-related AEs (TRAEs) occurred with pembrolizumab than paclitaxel (53% vs 84%).

Conclusion

In this long-term analysis, 2L pembrolizumab did not significantly improve OS but was associated with higher 24-month OS rates than paclitaxel. Pembrolizumab also increased OS benefit with PD-L1 enrichment among patients with PD-L1-positive gastric/GEJ cancer and led to fewer TRAEs than paclitaxel.

Trial registration

ClinicalTrials.gov, NCT02370498

中文翻译：

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派姆单抗与紫杉醇治疗既往治疗过的 PD-L1 阳性晚期胃癌或胃食管结合部癌：随机 3 期 KEYNOTE-061 试验的 2 年更新

背景

在 3 期 KEYNOTE-061 研究（截止日期：2017 年 10 月 26 日）中，与紫杉醇相比，派姆单抗在 PD-L1 联合阳性评分（CPS）≥1 胃癌/GEJ 癌中作为二线（2L）治疗没有显着延长 OS . 在额外两年的随访（截止日期：2019 年 7 月 10 日）后，我们展示了 CPS ≥ 1、≥ 5 和 ≥ 10 人群的结果。

方法

患者按 1:1 随机分配至派姆单抗 200 mg Q3W ≤ 35 个周期或标准剂量紫杉醇。主要终点：OS 和 PFS（CPS ≥ 1 人群）。使用分层 Cox 比例风险模型计算 HR。

结果

366/395 名 CPS ≥ 1 的患者 (92.7%) 死亡。在 CPS ≥ 1 人群中，派姆单抗与紫杉醇相比显示出改善 OS 的趋势（HR，0.81）；24 个月操作系统率：19.9% 对 8.5%。Pembrolizumab 通过 PD-L1 富集逐渐增加了 OS 获益（CPS ≥ 5：HR，0.72，24 个月率，24.2% 对 8.8%；CPS ≥ 10：0.69，24 个月率，32.1% 对 10.9%）。治疗组之间的中位 PFS 没有差异（CPS ≥ 1：HR，1.25；CPS ≥ 5：0.98；CPS ≥ 10：0.79）。ORR（派姆单抗 vs 紫杉醇）分别为 16.3% vs 13.6%（CPS ≥ 1）、20.0% vs 14.3%（CPS ≥ 5）和 24.5% vs 9.1%（CPS ≥ 10）；中位 DOR 分别为 19.1 个月对 5.2、32.7 对 4.8 个月和 NR 对 6.9。与紫杉醇相比，派姆单抗发生的治疗相关 AE (TRAE) 更少（53% 对 84%）。

结论

在这项长期分析中，2L 派姆单抗并未显着改善 OS，但与紫杉醇相比，其 24 个月 OS 率更高。Pembrolizumab 还通过 PD-L1 富集增加了 PD-L1 阳性胃癌 / GEJ 癌患者的 OS 益处，并且导致 TRAE 少于紫杉醇。

试用注册

ClinicalTrials.gov，NCT02370498