Pembrolizumab monotherapy provides durable anti-tumor activity and promotes overall survival (OS) in previously untreated advanced hepatocellular carcinoma patients. Nearly half of patients demonstrated some reduction in the size of their target lesion from baseline while on immunotherapy with the programmed death-1 inhibitor.
Previously, in cohort 1 of the open-label, single-arm, multi-country, Phase II KEYNOTE-224 trial, pembrolizumab monotherapy was shown to be efficacious and tolerable in patients with advanced hepatocellular carcinoma previously treated with sorafenib.
At the 2021 ASCO Gastrointestinal Cancers Symposium, lead author Jean-Luc Van Laethem, MD, PhD, of Hopital Erasme-Universite Libre de Bruxelles in Brussels, Belgium, presented data from cohort 2, which enrolled patients with advanced hepatocellular carcinoma and no prior systemic therapy (Abstract 297).
Research Details
A total of 51 patients were enrolled and treated with pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. The primary endpoint of the trial was objective response rate (ORR) with secondary endpoints of duration of response, disease control rate, time to progression (TTP), progression-free survival (PFS), OS, and safety. The median time from the first dose of therapy to data cutoff was 21 months.
Key eligibility criteria in this cohort included the following:
* the presence of radiologically, histologically, or cytologically confirmed, incurable hepatocellular carcinoma not amenable or refractory to locoregional therapy;
* measurable disease per RECIST 1.1 by blinded independent central review;
* Child-Pugh class A status;
* ECOG performance status of 0 or 1;
* a Barcelona Clinic Liver Cancer Stage B or C; and
* a life expectancy of 3 months or more.
Patients had a median age of 68 years and were mostly men (86%). About one-third of patients (37%) had an alpha-fetoprotein level higher than 200 ng/mL and about half (47%) reported alcohol use predisposing to hepatocellular carcinoma. Extrahepatic disease was present in about one-third (35%) and vascular invasion in 18 percent.
"If we look to the anti-tumor activity, the ORR was 16 percent, including eight patients with partial response. Median duration of response was not reached, while 70 percent were estimated to have response duration of at least 12 months," said Van Laethem.
"The percentage of patients with an objective response was generally similar across specified subgroups. And we observed reduction from baseline in tumor target lesion size in 22 of the 47 patients in course 2."
Median TTP was 4 months, median PFS was 4 months, and PFS rate at 12 months was 24 percent. The median overall survival was 17 months, and overall survival rate at 12 months was 58 percent, Van Laethem reported.
"If we look to the toxicity and tolerability, treatment-related adverse events occurred in 27 patients (53%). The most common ones were diarrhea (10%), fatigue (8%), hypothyroidism (8%), and myalgia (8%)," he said. Grade 3 or more treatment-related adverse events occurred in three patients, and one patient died.
In conclusion, Van Laethem noted: "In patients with advanced hepatocellular carcinoma and no prior systemic therapy, pembrolizumab monotherapy provided durable anti-tumor activity and promising overall survival. Safety profile with pembrolizumab was generally consistent with that previously observed for pembrolizumab in advance hepatocellular carcinoma in the second-line setting. These findings clearly support further evaluation of pembrolizumab-based regimens in the therapeutic landscape of hepatocellular carcinoma."
Mark L. Fuerst is a contributing writer.
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