Pembrolizumab shows durable efficacy in sorafenib-treated advanced HCC

Pembrolizumab has demonstrated durable efficacy and a manageable adverse event (AE) profile in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib in a 5-year follow-up of the KEYNOTE-224 study, according to data presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer 2022 (ESMO GI 2022).

The data, from 104 patients in the study’s cohort 1 (ie, patients who experienced disease progression after or were intolerant to sorafenib treatment), showed a median overall survival (OS) of 13.2 months and estimated 24-month and 36-month OS rates of 30.8 percent and 20.2 percent, respectively, after a median follow-up of 59.1 months. [Vogel A, et al, ESMO GI 2022, abstract SO-13]

Median progression-free survival (PFS) was 4.9 months, with an estimated 24-month PFS rate of 12.5 percent. Median time to disease progression was 4.8 months.

Overall response rate (ORR), the study’s primary endpoint, was 18.3 percent, while disease control rate was 61.5 percent. Complete response (CR) was achieved in 3.8 percent of patients (n=4), while 14.4 percent of patients (n=15) achieved partial response (PR) and 43.3 percent (n=45) had stable disease (SD).

The median duration of response was 21 months, with 77 percent of patients having a response lasting ≥12 months and 60.6 percent having a response lasting ≥18 months.

Notably, patients who achieved a response at first imaging assessment (n=11) had longer OS than nonresponders at first imaging assessment (n=87). Median OS was 53.1 months compared with 10.3 months, while estimated 24-month and 36-month OS rates were 81.8 percent vs 26.4 percent and 63.6 percent vs 16.1 percent, respectively.

The updated data showed that most treatment-related AEs were of low grade. Among 76 patients (73.1 percent) who reported treatment-related AEs, 26 patients (25 percent) experienced grade 3/4 events, and one patient (1 percent) experienced a grade 5 event. No new treatment-related deaths, immune-mediated hepatitis events, or virus-induced hepatitis flares were reported with extended follow-up.

“Long-term follow-up of KEYNOTE-224 demonstrated durable efficacy and manageable AEs with pembrolizumab in patients with sorafenib-treated advanced HCC,” the investigators noted.

In the nonrandomized, multicentre, open-label phase II trial, patients with sorafenib-treated advanced HCC with an Eastern Cooperative Oncology Group performance status of 0–1, adequate organ function, and Child-Pugh class A were treated with pembrolizumab 200 mg intravenously Q3W for about 2 years or until disease progression, unacceptable toxicity, patient withdrawal, or investigator decision.

Previously reported KEYNOTE-224 results, after a median follow-up of 12.3 months, showed an ORR of 17 percent (CR, 1 percent; PR, 16 percent; SD, 44 percent), median OS of 12.9 months, and median PFS of 4.9 months, with 12-month OS and PFS rates of 54 percent and 28 percent, respectively. [Lancet Oncol 2018;19:940-952] These results led to US FDA’s accelerated approval of pembrolizumab for sorafenib-treated HCC in November 2018. [https://www.fda.gov/drugs/fda-grants-accelerated-approval-pembrolizumab-hepatocellular-carcinoma]

More recently, the phase III KEYNOTE-394 trial (n=453) showed that combining pembrolizumab with best supportive care (BSC) improved OS (primary endpoint) vs BSC alone in second-line treatment of Asians with advanced HCC. In these patients previously treated with sorafenib or oxaliplatin-based chemotherapy, median OS was 14.6 months for pembrolizumab vs 13.0 for placebo (hazard ratio [HR], 0.79; p=0.0180), with 24-month OS rate of 34.3 percent vs 24.9 percent. [J Clin Oncol 2022;40(suppl4):383]