Search

Introduction: 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) or progression-free survival (PFS) superiority were not met at the final analysis. Outcomes based on an additional 18 months of follow-up are reported. Methods: 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 by blinded independent central review (BICR) per RECIST v1.1. Secondary endpoints included objective response rate (ORR), assessed by BICR per RECIST v1.1, and safety. Results: 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. Conclusion: 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.

Introduction: KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. Methods: Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. Results: The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6–4.1) versus 1.4 months (95% CI 1.4–2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32–0.70). The median OS was 13.8 months (95% CI 10.1–16.9) for pembrolizumab versus 8.3 months (95% CI 6.3–11.8) for placebo (HR 0.55; 95% CI 0.37–0.80). ORR was 20.6% (95% CI 13.4–29.5) for pembrolizumab versus 2.0% (95% CI 0.1–10.6) for placebo (difference: 18.5%; 95% CI 8.3–27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3–5 TRAEs, respectively. No treatment-related deaths occurred. Conclusion: Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.