Dr Lau on the Association of irAEs and OS in the HIMALAYA Study in HCC

George Lau, MD, FRCP, FAASLD, chairman, senior consultant, Gastroenterology and Hepatology, the Humanity and Health Medical Group, discusses the association between immune-related adverse effects (irAEs) and overall survival (OS) for patients with unresectable hepatocellular carcinoma (HCC) enrolled on the phase 3 HIMALAYA trial (NCT03298451).

At the 2023 ASCO Annual Meeting, investigators presented information on an exploratory analysis of the trial, revealing that patients treated the combination of durvalumab (Imfinzi) plus tremelimumab (Imjudo) experienced manageable and low-grade irAEs. Additionally, those who experienced irAEs achieved a numerical improvement in OS.

The median OS in patients who developed an irAE was 23.2 months (95% CI, 19.1-32.4) vs 14.1 months (95% CI, 11.6-17.9) in those patients who did not experience an irAE (HR, 0.727; 95% CI, 0.557-0.948). Moreover, the 6-months OS rates for patients who did and did not experience irAEs were 81.3% (95% CI, 75.1%-88.0%) vs 77.1% (95% CI, 72.1%-82.5%), respectively, and the 12-month OS rates were 69.1% (95% CI, 61.8%-77.2%) vs 55.2% (95% CI, 49.4%-61.8%), respectively.

Prior data from the trial showed that durvalumab/tremelimumab led to a 22% reduction in the risk of death vs sorafenib (Nexavar; HR, 0.78; 95% CI, 0.66-0.92; P = .0035), and these findings supported the FDA approval of the combination for the treatment of adult patients with HCC. However, one of the concerns of using 2 immune checkpoint inhibitors—specifically with a high dose of tremelimumab—was that the combination could lead to overactivation of the immune system and irAEs, Lau explains.

The OS difference based on the development of irAEs was similar for patients who were treated with durvalumab monotherapy, Lau expands. The median OS for those treated with durvalumab monotherapy who developed an irAE was 17.8 months (95% CI, 13.8-25.1) vs 16.5 months (95% CI, 13.1-19.4) for those who did not develop an irAE, Lau concludes.