Pembrolizumab led to improvement in overall survival compared to placebo in patients with advanced hepatocellular carcinoma previously treated with sorafenib.
Pembrolizumab (Keytruda) led to improvement in overall survival (OS) compared to placebo in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib, meeting the primary end point of the KEYNOTE-394 (NCT03062358) trial, according to a press release by Merck.
Pembrolizumab is an anti-PD-1 therapy that blocks the interaction between PD-1 and the PD-L1 and PD-L2 ligands. This activates T lymphocytes, which affects both tumor and healthy cells. Pembrolizumab has indications across multiple disease states including melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, colorectal cancer, and gastric cancer.
KEYNOTE-394 is a phase 3 randomized, parallel assignment trial with an actual enrollment of 454 participants and an estimated completion date of December 2022. The primary end point of the study is OS up to approximately 2 years. Secondary end points include progression-free survival (PFS), objective response rate (ORR), duration of response, disease control rate, time to progression, and the number of participants who experienced at least one adverse event (AE), and the number of participants who discontinued study treatment due to an AE.
During the study, patients were randomized into 1 of 2 arms. In the experimental arm, patients received an infusion of pembrolizumab on day 1 of each 3-week cycle for up to 35 cycles plus best supportive care. In the control arm, patients received a placebo on the first day of each 3-week cycle for up to 35 cycles of treatment plus best supportive care.
Preliminary results found that pembrolizumab and best supportive care statistically significantly improved OS compared with placebo. Additionally, the study also met its secondary end points of PFS, and ORR and no new safety signals were observed. Full results will be presented at an upcoming meeting.
“Frequently diagnosed at an advanced stage, hepatocellular carcinoma has one of the highest mortality rates of solid cancers. Despite recent progress, there remains an unmet need for anti-PD-1 monotherapy after sorafenib, where Keytruda is an established treatment option for patients,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “It is very encouraging that Keytruda significantly improved overall survival in this study, and we look forward to engaging with regulatory authorities as quickly as possible.”
In order to participate in the study, patients have had a confirmed HCC diagnosis, a Child-Pugh A liver score within 7 days prior to the first dose of study medication, a life expectancy of >3 months, at least one measurable lesion, an ECOG score of 0 or 1, documented radiographic progression, and must agree to use contraception. Patients who received sorafenib or oxaliplatin-based chemotherapy within 14 days of first dose, had esophageal or gastric variceal bleeding in the last 6 months, has a clinically apparent ascites on physical examination, has portal vein invasion at the main portal branch, has had a solid organ transplant, prior systemic therapy for HCC, or has an active infection requiring systemic therapy.