Findings from a phase 2 trial supported larger trials of the neoadjuvant antiprogrammed cell death protein 1 (PD-1) monotherapy, cemiplimab, for the treatment of hepatocellular carcinoma. These findings were published in The Lancet Gastroenterology and Hepatology.

This single-center, open-label, single-arm study recruited patients (N=21) with early-stage hepatocellular carcinoma from Mount Sinai Hospital in the United States in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT03916627). Patients received 2 cycles of 350 mg intravenous cemiplimab 3 weeks apart, underwent surgical resection, and received an additional 8 cycles of cemiplimab after recovering from surgery. The primary outcome was tumor necrosis and secondary endpoints were time to surgery and tumor features.

Patients were 86% men, 52% were Asian, cancer was stage II at screening among 67% of patients, and the most common causes of cancer were hepatitis B (38%) or C (23%) virus.


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The median time from cemiplimab initiation to surgery was 29 (IQR, 27-35) days. The longest time to surgery was 84 days. Surgery was aborted for 1 patient due to enlarged lymph nodes in the porta hepatis, which had not been visualized on imaging.

Complete tumor necrosis occurred among 15% of patients, >70% necrosis among 20% of patients, ³50% among 35% of patients, and <50% among 65% of patients.

Among the 2 patients with the largest tumor shrinkage, the degree of necrosis was underestimated in the imaging analysis compared with the pathological assessment.

Stratified by <50% and ³50% necrosis among all patients, tissue samples from those with <50% necrosis showed lower pretreatment B-cell (P =.00606), CD8 (P =.0121), cytotoxic (P =.0121), monocyte-derived macrophage (P =.0242), and activated or dysfunctional (P =.0424) signatures. In the post-treatment samples of these tissues, the <50% necrosis group showed lower CD8, activated or dysfunctional, cytotoxic, monocyte-derived (all P =.00606), B-cell (P =.0121), and regulatory T-cell (P =.0242) signatures.

Adverse events occurred among 29% of patients, presenting as grades 2 (14%), 3 (10%), or 1 (5%). No grades 4 or 5 events were observed. The most common events were fatigue (14%) and infusion-related reactions (10%).

This study was limited by the discrepancies between imaging and tissue analyses.

The study authors concluded that a PD-1-targeted monotherapy showed clinical activity among patients with early-stage hepatocellular carcinoma and supported continued evaluation of perioperative immunotherapy for this patient population.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Marron TU, Fiel MI, Hamon P, et al. Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022;7(3):219-229. doi:10.1016/S2468-1253(21)00385-X