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Pembrolizumab safe and efficacious in advanced hepatocellular carcinoma

Presented By
Prof. Shukui Qin, Nanjing University of Chinese Medicine, China
ASCO GI 2022
Phase 3, KEYNOTE-394
Pembrolizumab plus best supportive care outperformed placebo plus best supportive care in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) in the second-line treatment of patients with advanced hepatocellular carcinoma (HCC). Moreover, a meta-analysis of the phase 3 KEYNOTE-394 and KEYNOTE-240 trials provided support for global generalisability of the results [1].

Pembrolizumab, a PD-1 inhibitor, added to best supportive care demonstrated superiority over placebo plus best supportive care in a phase 2 (KEYNOTE-224; NCT02702414) and a phase 3 (KEYNOTE-240; NCT02702401) trial [2,3]. The current, multicentre, phase 3 KEYNOTE-394 study (NCT03062358) compared pembrolizumab with placebo in the second-line treatment for Asian patients with advanced HCC after sorafenib (90.7%) or chemotherapy. Patients received pembrolizumab (200 mg, every 3 weeks) plus best supportive care (n=300) or placebo plus best supportive care (n=153). OS was the primary endpoint of this trial. Prof. Shukui Qin (Nanjing University of Chinese Medicine, China) presented the results.

The median OS was significantly higher among patients who received pembrolizumab (14.6 vs 13.0 months; HR 0.79; P=0.0180). In addition, the 24-month OS rates were 34.3% in the pembrolizumab arm and 24.9% in the placebo arm. Similarly, the median PFS was higher in the pembrolizumab arm than in the placebo arm (2.6 vs 2.3 months; HR 0.74; P=0.0032). The 24-month PFS rates were 11.0% and 0%, favouring the pembrolizumab arm. The ORR was 12.7% for pembrolizumab receivers and 1.3% for placebo receivers. Furthermore, the median duration of response was 23.9 months in the pembrolizumab arm and 5.6 months in the placebo arm. A meta-analysis of the results of the KEYNOTE-394 and the KEYNOTE-240 trials showed an OS benefit for pembrolizumab receivers (median OS 14.2 vs 12.5 months; HR 0.79).

The safety analysis did not display unexpected issues. Any grade treatment-related adverse events (TRAEs) were reported in 66.9% and 49.7% of the patients in the pembrolizumab arm and the placebo arm, respectively. Grade 3 or higher TRAEs were observed in 14.4% of the pembrolizumab receivers and 5.9% of the placebo receivers. In addition, 3.0% of the patients in the pembrolizumab arm experienced grade 3 or higher immune-mediated AEs. In 5 cases, these events led to treatment discontinuation and in 1 case it resulted in death. “All in all, the safety profile of pembrolizumab was manageable and consistent with prior publications on this agent in this population,” concluded Dr Qin.

  1. Qin S, et al. Pembrolizumab Plus Best Supportive Care Versus Placebo Plus Best Supportive Care as Second-line Therapy in Patients in Asia With Advanced Hepatocellular Carcinoma: Phase 3 KEYNOTE-394 Study. Abstract 383, ASCO GI 2022, 20–22 January.

  2. Zhu AX, et al. Lancet. 2018;7:940–952.

  3. Finn RS, et al. J Clin Oncol. 2020;38(3):193–202.


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