Patient-reported outcomes from the phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

Abstract

4074 Background: In the Phase 3 HIMALAYA study (NCT03298451) of patients (pts) receiving first-line treatment for unresectable hepatocellular carcinoma (uHCC), a single priming dose of tremelimumab (T; anti-CTLA-4) plus durvalumab (D; anti-PD-L1) in the STRIDE regimen significantly improved overall survival (OS) vs sorafenib (S), and D monotherapy was noninferior to S for OS (Abou-Alfa et al. J Clin Oncol 2022;40[suppl 4]. Abs 379). Methods: A pre-planned secondary objective of HIMALAYA was to assess pt-reported outcomes (PROs) in pts receiving STRIDE (T 300 mg plus D 1500 mg [one dose] plus D 1500 mg once every 4 weeks [Q4W]; N=393) or D (1500 mg Q4W; N=389) vs S (400 mg twice daily; N=389). The European Organisation for Research and Treatment of Cancer (EORTC) 30-item Quality of Life (QoL) Questionnaire and the EORTC 18-item HCC QoL questionnaire were used to assess disease-related symptoms, physical functioning (PF), and Global Health Status (GHS)/QoL. Time to deterioration (TTD), defined as time from randomization to first clinically meaningful deterioration (worsening ≥10 points) confirmed at a subsequent visit or death, was assessed in pts with baseline scores ≤90 for symptoms or ≥10 for PF and GHS/QoL. Results: Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms. TTD in fatigue, appetite loss, abdominal pain, PF, and GHS/QoL were significantly longer for both STRIDE and D vs S (Table). TTD in nausea and abdominal swelling were significantly longer for STRIDE vs S. Conclusions: The positive OS outcomes for STRIDE and D in pts receiving first-line treatment for uHCC in HIMALAYA were associated with clinically meaningful, pt-centered benefits, demonstrated by delayed worsening of disease-related symptoms, PF, and GHS/QoL vs S. Median TTD in months (95% CI) in PROs for STRIDE and D vs S. Clinical trial information: NCT03298451. [Table: see text]