Outcomes by Comorbidities with Tremelimumab and Durvalumab in the Randomized, Controlled Phase 3 HIMALAYA Study in Unresectable Hepatocellular Carcinoma

Introduction: People with hepatocellular carcinoma (HCC) often have underlying comorbidities, which may impact prognosis and lead to safety challenges following treatment. This exploratory, post hoc analysis of the phase 3 HIMALAYA study (NCT03298451) assessed outcomes in participants with unresectable HCC and cardiovascular or metabolic comorbidities at baseline. Methods: Participants with unresectable HCC were randomized to STRIDE (Single Tremelimumab Regular Interval Durvalumab), durvalumab monotherapy, or sorafenib. Comorbidities were based on medical history assessed at baseline and qualified using preferred terms from cardiovascular or metabolic Standardised Medical Dictionary for Regulatory Activities Queries. Overall survival (OS) rates were evaluated in participants with or without cardiovascular or metabolic comorbidities within and by treatment group. The proportion of long-term survivors (alive ≥36 months post-randomization) and safety were assessed in participants with cardiovascular or metabolic comorbidities. Data cutoffs: August 27, 2021 (primary analysis); January 23, 2023 (4-year updated analysis, OS, and serious treatment-related adverse events). Results: Hypertension and type 2 diabetes mellitus were the most common cardiovascular and metabolic comorbidities, respectively. The 48-month OS rates with STRIDE were 28.0% and 21.7% in participants with and without cardiovascular comorbidities and 20.4% and 28.5% in those with and without metabolic comorbidities, respectively. In total, 28.2% of participants with cardiovascular comorbidities and 22.6% of participants with metabolic comorbidities experienced long-term survival with STRIDE. Safety in participants with cardiovascular or metabolic comorbidities was generally consistent with all participants in the safety analysis set; no new safety signals were observed. Conclusions: OS benefits with STRIDE were similar in participants with vs. without cardiovascular or metabolic comorbidities, with manageable safety in participants with comorbidities. These results support the durable benefits of STRIDE in a broad population reflective of unresectable HCC globally.