KEYNOTE-224: Pembrolizumab in Advanced Hepatocellular Carcinoma Pretreated With Sorafenib


Key Points

  • Objective response was observed in 17% of patients.
  • Duration of response was at least 9 months in 77% of responders.

As reported in The Lancet Oncology by Zhu et al, the phase II KEYNOTE-224 study has shown activity of pembrolizumab in advanced hepatocellular carcinoma (HCC) pretreated with sorafenib.

Study Details

In the study, 104 eligible patients who were intolerant of or progressed on sorafenib were enrolled in 10 countries between June 2016 and February 2017 and treated with pembrolizumab 200 mg every 3 weeks for approximately 2 years or until disease progression or unacceptable toxicity.


As of data cutoff in February 2018, median duration of follow-up was 12.3 months, and 17 patients (16%) were still receiving pembrolizumab. Objective response was observed in 18 patients (17%), including complete response in 1; 46 additional patients (44%) had stable disease; 6 patients (6%) had no postbaseline assessment and were considered nonevaluable. Median duration of response was not reached (range = 3.1–14.6+ months), with 12 responders (77%) having response of at least 9 months.

Adverse Events

Treatment-related adverse events occurred in 76 (73%) of 104 patients, including serious adverse events in 16 (15%) patients. Grade 3 or worse treatment-related events were reported in 27 patients (26%), with the most common being fatigue (4%), increased AST (7%), and increased ALT (4%); grade 4 hyperbilirubinemia occurred in 1 patient. Immune-mediated adverse events of any grade occurred in 15 patients (14%), with the most common being hypothyroidism (8%), adrenal insufficiency (3%), and hepatitis (3%); grade 3 events occurred in 4%. One death, due to ulcerative esophagitis, was attributed to treatment.

The investigators concluded, “Pembrolizumab was effective and tolerable in patients with advanced hepatocellular carcinoma who had previously been treated with sorafenib. These results indicate that pembrolizumab might be a treatment option for these patients. This drug is undergoing further assessment in two phase III, randomized trials as a second-line treatment in patients with hepatocellular carcinoma.”

The study was funded by Merck & Co, Inc.

Andrew X. Zhu, MD, of the Department of Medicine, Harvard Medical School, is the corresponding author for The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.