Drugs

Apr 17, 2025, 12:45

Tanja Obradovic: New developments in the frontline treatment of Metastatic Hepatocellular Carcinoma

Tanja Obradovic, Oncology Medical Strategy Advisor at Mercurial AI, shared on LinkedIn:

“Movements in the 1st line treatment of patients with metastatic hepatocellular carcinoma (mHCC)- FDA approval of Opdivo (nivolumab) and Yervoy (ipilimumab) combo, incoming new frontline options.

New Developments in the Frontline Treatment of Metastatic Hepatocellular Carcinoma (HCC)

On April 11th FDA approved Opdivo (nivolumab) plus Yervoy (ipilimumab) as a first-line treatment for adult patients with unresectable or metastatic hepatocellular carcinoma (HCC), based on the results from the Phase 3 randomized, open-label CheckMate-9DW trial (NCT04039607).

Results establish new standard of care and data is quite strong especially considering the strong performance of the control arm consisting of treatment with lenvatinib or sorafenib in the historical context. Median overall survival (mOS) with Opdivo plus Yervoy was 23.7 months (95% CI: 18.8-29.4) vs. 20.6 months (95% CI: 17.5-22.5) with lenvatinib or sorafenib (HR=0.79; 95% CI: 0.65-0.96 P=0.0180), reducing the risk of death by 21%.

Patient response rates was also high to Opdivo plus Yervoy, demonstrating an overall response rate (ORR) of 36.1% (95% CI: 31-41.5) compared to 13.2% (95% CI: 9.8-17.3; P<0.0001) of patients treated with lenvatinib or sorafenib (complete response 6.9% vs 1.8%; partial response 29.3% vs 11.4%).

Safety of the anti PD-1 Opdivo and anti-CTLA-4 Mab Yervoy combo followed profile previously observed so toxicity of the Yervoy is remaining a cautionary aspect of the combination with 27% of patients permanently discontinuing treatment due to toxicity.

This approval of the novel immunotherapy option is a very good news for the frontline HCC patients considering recent disappointing outcomes of negative LEAP-002 trial combining Keytruda and Lenvatinib and last month second complete response letter from FDA rejecting Elevar Therapeutics New Drug Application (NDA) for camrelizumab (anti PD-1 Ab) plus rivoceranib (VEGFR2-targeted TKI) combo in the first line HCC setting.

Additional anti-PD(L)-1 combinations are possibly coming into first line HCC treatment landscape with atezolizumab and bevacizumab with or without tiragolumab evaluated in SKYSCRAPER-14 trial (NCT05904886) with data readout likely in 2026.”

Tanja Obradovic: New developments in the frontline treatment of Metastatic Hepatocellular Carcinoma