Dr Kudo on Evaluating Nivolumab/Ipilimumab in Unresectable HCC

"Until now, atezolizumab plus bevacizumab has been a frequently used first-line regimen compared with durvalumab plus tremelimumab. But now, nivolumab plus ipilimumab [may] be the new choice of treatment because of the high efficacy outcomes and acceptable toxicity [profile]. [Additionally], the response rate, progression-free survival, and overall survival [with this regimen] are better than [those associated with] the other 2 regimens.”

Masatoshi Kudo, MD, PhD, a professor of gastroenterology and hepatology at Kindai University Faculty of Medicine, discussed findings from matching-adjusted indirect comparisons (MAICs) evaluating nivolumab (Opdivo) plus ipilimumab (Yervoy) vs durvalumab (Imfinzi) plus tremelimumab (Imjudo) and atezolizumab (Tecentriq) plus bevacizumab (Avastin) as first-line therapy for patients with unresectable hepatocellular carcinoma (HCC).

At the 2025 ESMO Gastrointestinal (GI) Cancers Congress Kudo presented findings from these analyses, which adjusted for differences in baseline characteristics across trial populations, showed that nivolumab plus ipilimumab was associated with higher overall response rates, longer progression-free survival, and improved overall survival compared with both durvalumab plus tremelimumab and atezolizumab plus bevacizumab. Kudo noted that the observed efficacy advantages, coupled with an acceptable toxicity profile, support consideration of nivolumab plus ipilimumab as a preferred first-line regimen for this patient population.

Historically, atezolizumab plus bevacizumab has been the most widely adopted first-line standard, with durvalumab plus tremelimumab serving as an alternative regimen. However, Kudo emphasized that these indirect comparison findings suggest that nivolumab plus ipilimumab could offer superior clinical outcomes compared with either of the other 2 regimens. Although MAICs are not a substitute for prospective, randomized, head-to-head trials, the consistency of benefit observed across efficacy end points reinforces the potential clinical relevance of these findings.

Immune-related adverse effects occurred with nivolumab plus ipilimumab but were generally manageable following established treatment guidelines.

He further noted that these findings could meaningfully influence treatment selection in the first-line setting for unresectable HCC, particularly in cases where maximizing response and survival is a priority. Although atezolizumab plus bevacizumab remains a valid option, and durvalumab plus tremelimumab offers another checkpoint inhibitor–based alternative, the potential for improved outcomes with nivolumab plus ipilimumab positions this regimen as a strong contender for routine clinical use.