FDA News

FDA approves Keytruda for patients with previously treated hepatocellular carcinoma

The FDA granted accelerated approval to pembrolizumab for the treatment of patients with hepatocellular carcinoma who received prior sorafenib.

The approval is the 14th indication for pembrolizumab (Keytruda, Merck), an anti-PD-1 therapy.

The FDA based the approval on results of the single-arm, open-label KEYNOTE-224 trial. The trial included 104 patients (median age, 68 years; 83% male; 81% white; 14% Asian) with HCC who experienced disease progression during or after sorafenib (Nexavar, Bayer) treatment or were intolerant to sorafenib.

All patients had ECOG performance status of 0 (61%) or 1 (39%), and all had Child-Pugh class A liver impairment (A5, 72%; A6, 22%; B7, 5%; and B8, 1%).

In addition, 21% were hepatitis B virus seropositive, 25% were hepatitis C virus seropositive and 9% were seropositive for both.

Sixty-four percent of patients had extrahepatic disease, 17% had vascular invasion and 9% had both.

Patients received pembrolizumab 200 mg every 3 weeks for up to 24 months, or until disease progression or unacceptable toxicity.

Objective response rate and duration of response served as the primary efficacy outcomes.

Median pembrolizumab exposure was 4.2 months (range, 1 day to 1.5 years).

Researchers reported an ORR of 17% (95% CI, 11-26), including a 1% complete response rate and 16% partial response rate.

Among the 18 patients who achieved a response, 16 (89%) remained in response for at least 6 months, and 10 (56%) remained in response for at least 12 months.

Adverse reactions among pembrolizumab-treated patients with HCC appeared similar to those observed in other studies of patients with melanoma or non-small cell lung cancer, with the exception of increased incidence of ascites (grade 3/grade 4, 8%) and immune-mediated hepatitis (2.9%).

Grade 3 or grade 4 laboratory abnormalities that occurred more frequently included elevated alanine transaminase (20%), elevated aspartate transaminase (9%) and hyperbilirubinemia (10%).

“Hepatocellular carcinoma is the most common type of liver cancer in adults, and [although] we have seen recent therapeutic advancements, there are still limited treatment options for advanced recurrent disease,” Andrew X. Zhu, MD, PhD, lead investigator of KEYNOTE-224, director of liver cancer research at Massachusetts General Hospital and professor of medicine at Harvard Medical School, said in a Merck-issued press release. “[This] approval of Keytruda is important, as it provides a new treatment option for patients with hepatocellular carcinoma who have been previously treated with sorafenib.”

The FDA previously approved pembrolizumab for treatment of certain patients with melanoma, lung cancer, head and neck cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, gastric cancer, cervical cancer and microsatellite instability-high cancers.

The FDA granted accelerated approval to pembrolizumab for the treatment of patients with hepatocellular carcinoma who received prior sorafenib.

The approval is the 14th indication for pembrolizumab (Keytruda, Merck), an anti-PD-1 therapy.

The FDA based the approval on results of the single-arm, open-label KEYNOTE-224 trial. The trial included 104 patients (median age, 68 years; 83% male; 81% white; 14% Asian) with HCC who experienced disease progression during or after sorafenib (Nexavar, Bayer) treatment or were intolerant to sorafenib.

All patients had ECOG performance status of 0 (61%) or 1 (39%), and all had Child-Pugh class A liver impairment (A5, 72%; A6, 22%; B7, 5%; and B8, 1%).

In addition, 21% were hepatitis B virus seropositive, 25% were hepatitis C virus seropositive and 9% were seropositive for both.

Sixty-four percent of patients had extrahepatic disease, 17% had vascular invasion and 9% had both.

Patients received pembrolizumab 200 mg every 3 weeks for up to 24 months, or until disease progression or unacceptable toxicity.

Objective response rate and duration of response served as the primary efficacy outcomes.

Median pembrolizumab exposure was 4.2 months (range, 1 day to 1.5 years).

Researchers reported an ORR of 17% (95% CI, 11-26), including a 1% complete response rate and 16% partial response rate.

Among the 18 patients who achieved a response, 16 (89%) remained in response for at least 6 months, and 10 (56%) remained in response for at least 12 months.

Adverse reactions among pembrolizumab-treated patients with HCC appeared similar to those observed in other studies of patients with melanoma or non-small cell lung cancer, with the exception of increased incidence of ascites (grade 3/grade 4, 8%) and immune-mediated hepatitis (2.9%).

Grade 3 or grade 4 laboratory abnormalities that occurred more frequently included elevated alanine transaminase (20%), elevated aspartate transaminase (9%) and hyperbilirubinemia (10%).

“Hepatocellular carcinoma is the most common type of liver cancer in adults, and [although] we have seen recent therapeutic advancements, there are still limited treatment options for advanced recurrent disease,” Andrew X. Zhu, MD, PhD, lead investigator of KEYNOTE-224, director of liver cancer research at Massachusetts General Hospital and professor of medicine at Harvard Medical School, said in a Merck-issued press release. “[This] approval of Keytruda is important, as it provides a new treatment option for patients with hepatocellular carcinoma who have been previously treated with sorafenib.”

The FDA previously approved pembrolizumab for treatment of certain patients with melanoma, lung cancer, head and neck cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, gastric cancer, cervical cancer and microsatellite instability-high cancers.

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