Impact of comedication on survival and toxicity in patients treated with systemic therapy for unresectable hepatocellular carcinoma

Abstract

Introduction This study aims to evaluate the association between concomitant medication, survival and toxicity in patients with unresectable hepatocellular carcinoma (uHCC) treated with systemic therapy. Methods All uHCC patients treated with atezolizumab plus bevacizumab or durvalumab plus tremelimumab in our center were included. Endpoints were progression-free survival (PFS), HCC-specific survival, grade ≥4 adverse events (AE) and treatment-related discontinuation. Results One hundred and five patients were included, 88 treated with atezolizumab plus bevacizumab and 17 with durvalumab plus tremelimumab. The most common prescribed concomitant medication was cardiovascular drugs (62%). Median PFS and HCC-specific survival were 6.0 (95% CI 4.0–12.0) and 19.0 months (95% CI 14.0–25.0) for atezolizumab plus bevacizumab versus 5.0 (95% CI 2.0–19.0) and 17.0 months (95% CI 7.0–21.0) for durvalumab plus tremelimumab, respectively. Five (6%) and 4 (24%) patients presented at least one grade ≥4 AE, respectively (P = 0.04). Grade ≥4 AE and treatment-related discontinuation were more frequent in patients with at least one psycholeptic or psychoanaleptic drug (17% vs 3%, P = 0.03 and 12% vs 2%, P = 0.03). Conclusions In this real-world cohort of patients with uHCC, baseline concomitant medication was not significantly associated with PFS or HCC-specific survival. Psycholeptic or psychoanaleptic drug intake was associated with grade ≥4 AE and treatment-related discontinuation, but these findings should be considered hypothesis-generating because of the retrospective design, small sample size and potential confounding.