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]

PD-1/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy

“…The median overall survival (OS) in both groups was 13.8 months versus 16.4 months, meeting the primary endpoint; PFS was 3.78 months versus 4.07 months, ORR was 20.1% VS 5.1%; DOR was 22.34 months vs 18.43 months; DCR was 60.1% vs 60.7%, and the incidence of treatment-related adverse events of grade 3 or 4 was 25.8% vs 36.9%. Based on these results, AstraZeneca announced an application to the US Food and Drug Administration for approval of the STRIDE regimen that applies durvalumab plus tremelimumab as a first-line treatment for unresectable HCC ( 142 ).…”

Complete Pathologic Response to Gemcitabine and Oxaliplatin Chemotherapy After Prior Therapies in a Patient With Hepatocellular Carcinoma and Peritoneal Metastases Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

“…Alternatively, in patients who are ineligible for combination therapy with atezolizumab and bevacizumab or durvalumab and tremelimumab, durvalumab monotherapy may also be an acceptable alternative to sorafenib [ 19 ]. Quality of life assessments also demonstrated significant improvement in time to deterioration from disease-related symptoms of both durvalumab/tremelimumab and durvalumab alone, compared with sorafenib [ 21 ].…”

Systemic therapies in hepatocellular carcinoma: A revolution?

“…Similarly, ramucirumab (an IgG1 monoclonal antibody that inhibits ligand activation of VEGFR‐2) showed to improve overall survival (OS) in patients with α ‐fetoprotein >400 ng/mL in the REACH‐2 14 . The potential of immunotherapy was vividly showcased in trials like IMbrave150 15,16 and HIMALAYA 17,18 followed by the CARES‐310 19 in advanced HCC and encouraging in the IMbrave050 as adjuvant treatment 20 . However, the primary aim of IMbrave050 20 is recurrence‐free survival and not OS as in the other clinical trials (CT) mentioned above.…”