The U.S. Food and Drug Administration (FDA) has approved Keytruda (pembrolizumab) as a treatment for patients with hepatocellular carcinoma (HCC) — the most common type of liver cancer — who previously had received Nexavar (sorafenib).
The accelerated approval was based on tumor response rates and duration of responses seen in the open-label KEYNOTE-224 Phase 2 trial (NCT02702414). Continued approval of Keytruda is dependent on further confirmation of the drug’s clinical benefit.
“Hepatocellular carcinoma is the most common type of liver cancer in adults, and while we have seen recent therapeutic advancements, there are still limited treatment options for advanced recurrent disease,” Andrew X. Zhu, lead investigator, and director of liver cancer research at Massachusetts General Hospital, said in a press release. “[The] approval of Keytruda is important, as it provides a new treatment option for patients with hepatocellular carcinoma who have been previously treated with sorafenib.”
Keytruda is an immunotherapy developed by Merck (known as MSD outside the U.S. and Canada) that inhibits PD-L1, a molecule produced by cancer cells that helps them escape from the immune system. By inhibiting PD-L1, Keytruda enhances the natural response of the body against the tumor.
The KEYNOTE-224 Phase 2 trial was designed to determine whether Keytruda was feasible for HCC patients who lacked treatment options after Sorafenib — the standard of care for HCC — failed to improve their condition.
The trial included 104 patients, median age 68, most of whom were men (83%), white (81%), and with metastasis (64%). Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection — two major drivers of liver cancer — were eligible for the trial.
Participants received Keytruda for two years or until their disease worsened or they experienced intolerable toxicity. Researchers measured the size of the patients’ tumors every nine weeks.
After a median 4.2 months on Keytruda, 17% of patients had responded to the treatment, including 1% whose tumors disappeared. Among those who responded, 89% had responses lasting six months or more and 56% lasting one year or more.
Patients experienced side effects similar to those in other Keytruda trials, such as anemia and elevated liver enzymes. Some side effects, however, were exclusive of HCC patients and included fluid accumulation in the abdomen and hepatitis.
“The approval of Keytruda for advanced hepatocellular carcinoma marks the second FDA approval for hepatocellular carcinoma in Merck’s oncology portfolio this year, underscoring our commitment to help bring forward new treatment options for cancers that have historically been very challenging to treat,” said Scot Ebbinghaus, vice president of clinical research at Merck. “We look forward to continuing to advance research for hepatocellular carcinoma across our portfolio with the goal to help even more patients affected by this type of cancer.”
KEYNOTE-224 is also studying the efficacy of Keytruda as a first-line treatment for HCC. Both arms of the trial are ongoing; the estimated completion date is May 2021.