The final results from the Phase 3 KEYNOTE-394 trial have been announced. This trial investigated pembrolizumab, an anti-PD-1 therapy, plus best supportive care (BSC) in patients in Asia with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib.
KEYNOTE-394 is the first trial with an anti-PD-1/L1 as a second-line monotherapy treatment to show an improvement in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) compared to placebo plus BSC for these patients.
These data add to the body of evidence relating to the use of pembrolizumab as a monotherapy in second-line HCC post sorafenib.
Pembrolizumab plus BSC demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of OS, reducing the risk of death by 21% (HR=0.79 [95% CI, 0.63-0.99]; p=0.0180) compared to placebo plus BSC for patients with previously treated advanced HCC.
For patients treated with pembro plus BSC, median OS was 14.6 months (95% CI, 12.6-18.0) compared to 13.0 months (95% CI, 10.5-15.1) for patients treated with placebo plus BSC.
The percentage of patients who were alive at two years was 34.3% for pembrolizumab plus BSC compared to 24.9% for placebo plus BSC. These data will be presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium on Friday, Jan. 21 at 10:15 a.m. ET.
“Hepatocellular carcinoma is a leading cause of cancer death across the world, and there are limited treatment options shown to extend survival for patients following treatment with sorafenib,” said Dr. Shukui Qin, director, Cancer Center of Jinling Hospital, and professor, Nanjing University of Chinese Medicine. “These overall survival data are very encouraging for patients with HCC previously treated with sorafenib and show the potential of KEYTRUDA to extend the lives of these patients.”
Treatment-related adverse events (TRAEs) occurred in 66.9% of patients in the pembrolizumab plus BSC arm and 49.7% of patients in the placebo plus BSC arm, and Grade 3-5 TRAEs occurred in 14.4% of patients in the pembrolizumab plus BSC arm and 5.9% of patients in placebo plus BSC arm.
Immune-mediated adverse events (AEs) of any grade occurred in 18.1% of patients receiving pembrolizumab plus BSC and 10.5% of patients receiving placebo plus BSC.
Grade 3-5 immune-mediated AEs occurred in 3.0% of patients receiving pembrolizumab plus BSC. There were three deaths (due to gastrointestinal haemorrhage, autoimmune hepatitis, and soft tissue infection) in the pembrolizumab arm related to the study intervention.
“Patients with advanced HCC still have a high unmet medical need with low survival rates, reinforcing the need for treatment options that can improve overall survival,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories.
“We are pleased to share these new data from pembrolizumab and are committed to advancing research for patients with this difficult-to-treat cancer through our broad global program in HCC.”
In the U.S., pembrolizumab is indicated for the treatment of patients with HCC who have been previously treated with sorafenib based on ORR and duration of response (DOR) data from KEYNOTE-224.
This indication is approved under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Data from KEYNOTE-394 are being discussed with global regulatory authorities and will be evaluated as a potential confirmatory study in the U.S.
Merck is dedicated to advancing research in HCC and has a global development program of seven clinical trials that have enrolled or are expected to enroll approximately 3,000 patients. In HCC, pembrolizumab is being studied across multiple settings and lines of therapy as monotherapy and in combination with other treatments, including therapies through our collaborations.