Durvalumab plus tremelimumab prolongs survival with tolerable safety in liver cancer
Improved overall survival was demonstrated with the combination of durvalumab and tremelimumab in patients with unresectable liver cancer treated in the phase 3 HIMALAYA study.
Treatment with either a single dose combination of tremelimumab with durvalumab at regular intervals (Imfinzi), the STRIDE regimen, or durvalumab alone has shown improved overall survival compared to sorafenib (Nexavar ) in patients with unresectable liver cancer, according to results from the Phase 3 HIMALAYA trial (NCT03298451).1
“The HIMALAYA results show a consistent survival benefit with the STRIDE diet in patients with unresectable liver cancer, regardless of baseline liver function reserve. These important subgroup analyzes add to the body of evidence demonstrating the potential of Imfinzi combinations to significantly improve outcomes for those patients who need effective and generally well-tolerated treatments,” said Cristian Massacesi, AstraZeneca Chief Medical Officer and Director of Oncology Development .
A sub-review presented at both ESMO World GI 2022 and EASL 2022 explored the safety of STRIDE and durvalumab treatments at baseline liver function. Investigators measured liver function using the ALBI (albumin-bilirubin) scoring system. This scoring system assesses the level of severe liver dysfunction from grades 1 to 3.
Hazard ratios (HR) for overall survival (OS) were consistent with the primary analysis in the ALBI grade 1 group (HR 0.79; 95% CI, 0.62-1.01) and the ALBI group grade 2/3 (HR 0.83; 95% CI 0.65 -1.05) regardless of baseline liver function scores. STRIDE results were consistent for overall response rate, duration of response, and measures of tolerance, regardless of ALBI score. Patients who received STRIDE treatment and remained on the trial saw stable liver function over time
A self-reported questionnaire was also used to assess the impact of treatment status on health-related quality of life. Also presented at EASL 2022, questionnaire results revealed that patients who received the STRIDE diet had fewer moderate to severe instances of mobility, self-care, discomfort, anxiety, and depression than those who received the STRIDE diet. who received sorafenib. Deteriorating health contributed to more treatment discontinuations than disease progression. Investigators found that after stopping treatment, more patients experienced moderate to extreme problems in all health-related quality of life domains. These results confirm the benefits of the STRIDE regimen in terms of quality of life, particularly for patients who remain on treatment.
The HIMALAYA study was a randomized, open-label, multicenter study. Investigators administered STRIDE treatment using a priming dose of 300 mg tremelimumab with 1500 mg durvalumab followed by regular durvalumab every 4 weeks. The trial included 1324 patients with advanced unresectable hepatocellular carcinoma who had not been treated with prior systemic therapy and who were not eligible for locoregional treatment of the liver and surrounding tissues. The primary endpoint was OS for STRIDE versus sorafenib, and secondary endpoints were OS for durvalumab monotherapy versus sorafenib, objective response rate and progression-free survival for STRIDE and durvalumab alone.
Key findings from HIMALAYA were presented earlier this year at the American Society of Clinical Oncology’s 2022 Symposium on Gastrointestinal Cancers in January. The results indicated that the trial met its primary endpoint, showing substantial improvement in OS associated with the STRIDE treatment regimen. The safety profiles of STRIDE and durvalumab monotherapy were consistent with previous profiles, and no new safety signals were identified.
Investigators randomized 1171 patients to receive STRIDE (n=393), durvalumab alone (n=389), or sorafenib (n=389). The median OS was 16.43 months (95% CI, 14.16-19.58) for patients receiving STRIDE, 16.56 months (95% CI, 14.06-19.12) for those receiving durvalumab monotherapy and 13.77 months (95% CI, 12.25-16.13) for patients receiving sorafenib. At 36 months, OS was 30.7% for the STRIDE group, 24.7% for the durvalumab group and 20.2% for the sorafenib group. The OS HR for STRIDE vs sorafenib was 0.78 (96.02% CI, 0.65-0.93; P = 0.0035) and for durvalumab alone versus sorafenib it was 0.86 (95.67% CI, 0.73-1.03; non-inferiority margin, 1.08).
Grade 3/4 treatment-related adverse events were reported in 50.5% of patients with STRIDE, 37.1% with durvalumab, and 52.4% with sorafenib.2
The HIMALAYA study is ongoing and actively recruiting at 181 centers in 16 countries, spanning the United States, Canada, Europe, South America and Asia.
1. AstraZeneca shares data at EASL and ESMO World GI for combinations of Imfinzi in patients with liver and biliary cancers. Press release. Astra Zeneca; July 1, 2022. Accessed July 6, 2022. https://bit.ly/3yJrTUv
2. Abu-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. N Eng J Med. June 6, 2022. doi: https://doi.org/10.1056/EVIDoa2100070