Positive results from the HIMALAYA phase III trial showed a single priming dose of tremelimumab added to Imfinzi (durvalumab) demonstrated a statistically significant and clinically meaningful improvement in overall survival versus Nexavar (sorafenib) as a first-line treatment for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy and were not eligible for localized treatment.
Imfinzi is sponsored by AstraZeneca.
This novel dose and schedule of Imfinzi and tremelimumab, an anti-CTLA4 antibody, is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab) (The Cancer Letter, Oct. 22, 2021). Results from the trial will be presented on Jan. 21 at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
Patients treated with the STRIDE regimen experienced a 22% reduction in the risk of death versus Nexavar (HR 0.78; 96.02% CI 0.65-0.93; p=0.0035). Median OS was 16.4 months versus 13.8 for Nexavar. An estimated 31% of patients were still alive at three years versus 20% for Nexavar.
Results also showed an increase in objective response rate with the STRIDE regimen versus Nexavar (20.1% vs. 5.1%). Median duration of response was 22.3 months with the STRIDE regimen versus 18.4 with Nexavar. The addition of tremelimumab to Imfinzi did not increase severe liver toxicity, and no bleeding risk was observed.
HIMALAYA also tested Imfinzi monotherapy, which demonstrated non-inferior OS to Nexavar (HR 0.86; 95.67% CI 0.73-1.03; non-inferiority margin 1.08) with a median OS of 16.6 months versus 13.8, and an improved tolerability profile versus Nexavar.
The safety profiles of the STRIDE regimen and for Imfinzi alone were consistent with the known profiles of each medicine, and no new safety signals were identified. Grade 3 or 4 treatment-related adverse events were experienced by 25.8% of patients treated with the STRIDE regimen and by 12.9% of patients treated with Imfinzi alone, versus 36.9% of patients on Nexavar.
Incidence of grade 3 or 4 treatment-related hepatic events were low across treatment arms (5.9% for the STRIDE regimen and 5.2% for Imfinzi, versus 4.5% for Nexavar). Treatment-related AEs led to treatment discontinuation in 8.2% of patients treated with the STRIDE regimen and 4.1% of patients treated with Imfinzi alone, versus 11% for Nexavar.
An additional presentation featured during the ASCO Gastrointestinal Cancers Symposium will showcase Imfinzi data from the TOPAZ-1 phase III trial, demonstrating the potential of this medicine in the treatment of advanced biliary tract cancer.
