PDF(Pubmed)
Abstract：
UNASSIGNED: KEYNOTE-240 showed a favorable benefit/risk profile for pembrolizumab versus placebo in patients with sorafenib-treated advanced hepatocellular carcinoma (HCC); however, prespecified statistical significance criteria for overall survival (OS) and progression-free survival (PFS) superiority were not met at the final analysis. Outcomes based on an additional 18 months of follow-up are reported.
UNASSIGNED: Adults with sorafenib-treated advanced HCC were randomized 2:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo. Dual primary endpoints were OS and PFS assessed per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included objective response rate (ORR), assessed per RECIST v1.1 by BICR, and safety.
UNASSIGNED: 413 patients were randomized (pembrolizumab, n = 278; placebo, n = 135). As of July 13, 2020, median (range) time from randomization to data cutoff was 39.6 (31.7-48.8) months for pembrolizumab and 39.8 (31.7-47.8) months for placebo. Estimated OS rates (95% CI) were 17.7% (13.4-22.5%) for pembrolizumab and 11.7% (6.8-17.9%) for placebo at 36 months. The estimated PFS rate (95% CI) for pembrolizumab was 8.9% (5.3-13.6%) and 0% for placebo at 36 months. ORR (95% CI) was 18.3% (14.0-23.4%) for pembrolizumab and 4.4% (1.6-9.4%) for placebo. Immune-mediated hepatitis events did not increase with follow-up. No viral hepatitis flare events were reported.
UNASSIGNED: With extended follow-up, pembrolizumab continued to maintain improvement in OS and PFS and was associated with a consistent adverse event profile compared with placebo in patients with sorafenib-treated advanced HCC. Although KEYNOTE-240 did not meet prespecified statistical significance criteria at the final analysis, these results together with the antitumor activity of second-line pembrolizumab observed in KEYNOTE-224 and the statistically significant and clinically meaningful OS and PFS benefits of second-line pembrolizumab in patients from Asia observed in KEYNOTE-394 reinforce the clinical activity of pembrolizumab in previously treated patients with advanced HCC.
UNASSIGNED: Adults with sorafenib-treated advanced HCC were randomized 2:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo. Dual primary endpoints were OS and PFS assessed per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included objective response rate (ORR), assessed per RECIST v1.1 by BICR, and safety.
UNASSIGNED: 413 patients were randomized (pembrolizumab, n = 278; placebo, n = 135). As of July 13, 2020, median (range) time from randomization to data cutoff was 39.6 (31.7-48.8) months for pembrolizumab and 39.8 (31.7-47.8) months for placebo. Estimated OS rates (95% CI) were 17.7% (13.4-22.5%) for pembrolizumab and 11.7% (6.8-17.9%) for placebo at 36 months. The estimated PFS rate (95% CI) for pembrolizumab was 8.9% (5.3-13.6%) and 0% for placebo at 36 months. ORR (95% CI) was 18.3% (14.0-23.4%) for pembrolizumab and 4.4% (1.6-9.4%) for placebo. Immune-mediated hepatitis events did not increase with follow-up. No viral hepatitis flare events were reported.
UNASSIGNED: With extended follow-up, pembrolizumab continued to maintain improvement in OS and PFS and was associated with a consistent adverse event profile compared with placebo in patients with sorafenib-treated advanced HCC. Although KEYNOTE-240 did not meet prespecified statistical significance criteria at the final analysis, these results together with the antitumor activity of second-line pembrolizumab observed in KEYNOTE-224 and the statistically significant and clinically meaningful OS and PFS benefits of second-line pembrolizumab in patients from Asia observed in KEYNOTE-394 reinforce the clinical activity of pembrolizumab in previously treated patients with advanced HCC.
摘要：
■KEYNOTE-240在索拉非尼治疗的晚期肝细胞癌（HCC）患者中，与安慰剂相比，pembrolizumab具有良好的获益/风险特征；然而，最终分析未达到预设的总生存期(OS)和无进展生存期(PFS)优势的统计学显著性标准.报告了基于额外18个月随访的结果。
■使用索拉非尼治疗的晚期HCC的成年人被随机分为2：1，每3周静脉注射200mgpembrolizumab或安慰剂。双重主要终点是根据RECISTv1.1通过盲法独立中央审查（BICR）评估的OS和PFS。次要终点包括客观反应率（ORR），BICR根据RECISTV1.1评估，和安全。
■413例患者被随机分组(pembrolizumab，n=278；安慰剂，n=135)。截至2020年7月13日，从随机分组到数据截止的中位（范围）时间为39.6（31.7-48.8）个月，安慰剂为39.8（31.7-47.8）个月。36个月时，pembrolizumab的估计OS率（95％CI）为17.7％（13.4-22.5％），安慰剂为11.7％（6.8-17.9％）。36个月时，pembrolizumab的估计PFS率（95％CI）为8.9％（5.3-13.6％），安慰剂为0％。Pembrolizumab的ORR（95％CI）为18.3％（14.0-23.4％），安慰剂为4.4％（1.6-9.4％）。免疫介导的肝炎事件没有增加随访。未报告病毒性肝炎事件。
■通过延长随访，在索拉非尼治疗的晚期HCC患者中,与安慰剂相比,派姆单抗继续维持OS和PFS的改善,并且与一致的不良事件情况相关.尽管KEYNOTE-240在最终分析中不符合预设的统计显著性标准，这些结果加上在KEYNOTE-224中观察到的二线派姆单抗的抗肿瘤活性,以及在KEYNOTE-394中观察到的二线派姆单抗在亚洲患者中的统计学显著和临床意义的OS和PFS获益,增强了派姆单抗在先前治疗过的晚期HCC患者中的临床活性.
■使用索拉非尼治疗的晚期HCC的成年人被随机分为2：1，每3周静脉注射200mgpembrolizumab或安慰剂。双重主要终点是根据RECISTv1.1通过盲法独立中央审查（BICR）评估的OS和PFS。次要终点包括客观反应率（ORR），BICR根据RECISTV1.1评估，和安全。
■413例患者被随机分组(pembrolizumab，n=278；安慰剂，n=135)。截至2020年7月13日，从随机分组到数据截止的中位（范围）时间为39.6（31.7-48.8）个月，安慰剂为39.8（31.7-47.8）个月。36个月时，pembrolizumab的估计OS率（95％CI）为17.7％（13.4-22.5％），安慰剂为11.7％（6.8-17.9％）。36个月时，pembrolizumab的估计PFS率（95％CI）为8.9％（5.3-13.6％），安慰剂为0％。Pembrolizumab的ORR（95％CI）为18.3％（14.0-23.4％），安慰剂为4.4％（1.6-9.4％）。免疫介导的肝炎事件没有增加随访。未报告病毒性肝炎事件。
■通过延长随访，在索拉非尼治疗的晚期HCC患者中,与安慰剂相比,派姆单抗继续维持OS和PFS的改善,并且与一致的不良事件情况相关.尽管KEYNOTE-240在最终分析中不符合预设的统计显著性标准，这些结果加上在KEYNOTE-224中观察到的二线派姆单抗的抗肿瘤活性,以及在KEYNOTE-394中观察到的二线派姆单抗在亚洲患者中的统计学显著和临床意义的OS和PFS获益,增强了派姆单抗在先前治疗过的晚期HCC患者中的临床活性.
