目的:Pembrolizumab在KEYNOTE-059(第三行或以上)的程序性死亡配体1阳性(联合阳性评分(CPS)≥1)胃/胃食管交界癌中显示出抗肿瘤活性,KEYNOTE-061(第二行),和KEYNOTE-062(第一行)。在这些研究中,我们在日本患者的几种疗法中表征了pembrolizumab单药治疗的疗效和安全性。
方法:这项分析是在KEYNOTE-059队列1(均为派姆单抗)的34例患者中进行的,包括13例CPS≥1的患者,65例CPS≥1的患者来自KEYNOTE-061(pembrolizumab,n=27;化疗,n=38),和70例来自KEYNOTE-062的CPS≥1的患者(pembrolizumab,n=38;化疗,n=32)。总生存期(OS),无进展生存期(PFS),客观反应率(ORR),并对安全性进行了评估。
结果:在KEYNOTE-059中,pembrolizumab的ORR为9%,中位PFS为2个月,中位OS为10个月。在KEYNOTE-061中,pembrolizumab的中位OS为12个月,而化疗的中位OS为10个月(风险比(HR),0.67;95%置信区间(CI),0.39-1.15)。PFS中位数(pembrolizumabvs.化疗)为2个月与4个月(HR,1.21;95%CI,0.69-2.13);ORR为7%对18%。在KEYNOTE-062中,派姆单抗的中位OS为20个月,而化疗的中位OS为18个月(HR,0.76;95%CI,0.43-1.33)。PFS中位数(pembrolizumabvs.化疗)为6个月与7个月(HR,1.03;95%CI,0.61-1.74);ORR为29%对34%。
结论:目前的分析提供了有价值的信息,表明抗PD-1治疗胃癌值得进一步评估。
背景:ClinicalTrials.gov:NCT02335411(KEYNOTE-059),NCT02370498(KEYNOTE-061),和NCT02494583(KEYNOTE-062)。
OBJECTIVE: Pembrolizumab demonstrated antitumor activity in programmed death ligand 1 positive (combined positive score (CPS) ≥ 1) gastric/gastroesophageal junction cancer in KEYNOTE-059 (third line or beyond), KEYNOTE-061 (second line), and KEYNOTE-062 (first line). We characterized efficacy and safety of pembrolizumab monotherapy in Japanese patients across several lines of therapy in these studies.
METHODS: This analysis was conducted in 34 patients from KEYNOTE-059 cohort 1 (all pembrolizumab), including 13 patients with CPS ≥ 1, 65 patients with CPS ≥ 1 from KEYNOTE-061 (pembrolizumab, n = 27; chemotherapy, n = 38), and 70 patients with CPS ≥ 1 from KEYNOTE-062 (pembrolizumab, n = 38; chemotherapy, n = 32). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were evaluated.
RESULTS: In KEYNOTE-059, ORR with pembrolizumab was 9%, median PFS was 2 months, and median OS was 10 months. In KEYNOTE-061, median OS was 12 months with pembrolizumab versus 10 months with chemotherapy (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.39-1.15). Median PFS (pembrolizumab vs. chemotherapy) was 2 months versus 4 months (HR, 1.21; 95% CI, 0.69-2.13); ORR was 7% versus 18%. In KEYNOTE-062, median OS was 20 months with pembrolizumab versus 18 months with chemotherapy (HR, 0.76; 95% CI, 0.43-1.33). Median PFS (pembrolizumab vs. chemotherapy) was 6 months versus 7 months (HR, 1.03; 95% CI, 0.61-1.74); ORR was 29% versus 34%.
CONCLUSIONS: The current analysis provides valuable information that anti-PD-1 therapies are worthy of further assessment for gastric cancer.
BACKGROUND: ClinicalTrials.gov: NCT02335411 (KEYNOTE-059), NCT02370498 (KEYNOTE-061), and NCT02494583 (KEYNOTE-062).