Improvement in overall survival has been demonstrated with the combination of durvalumab and tremelimumab in patients with unresectable liver cancer treated in the phase 3 HIMALAYA study.
Treatment with either the combination of single dose tremelimumab with regular interval durvalumab (Imfinzi) or the STRIDE regimen or durvalumab alone showed an improvement overall survival compared with 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 regimen in patients with unresectable liver cancer regardless of baseline liver functional reserve. These important subgroup analyses add to the body of evidence demonstrating the potential for Imfinzi combinations to meaningfully improve outcomes for these patients who are in need of effective and generally well tolerated treatments,” said Cristian Massacesi, AstraZeneca’s chief medical officer and oncology chief development officer.
A sub-analysis 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 disfunction from grades 1 to 3.
The overall survival (OS) hazard ratios (HR) were consistent with the primary analysis in the ALBI grade 1 group (HR 0.79; 95% CI, 0.62-1.01) and ALBI grade 2/3 group (HR 0.83; 95% CI 0.65-1.05) regardless of baseline liver function scores. STRIDE results were found consistent across overall response rate, duration of response, and tolerance measures regardless of ALBI score. Patients who received STRIDE treatment and remained on trial saw stable liver function over time
A self-reported questionnaire was also used to assess treatment status impact on health-related quality of life. Also presented at EASL 2022, the questionnaire results revealed that patients who received the STRIDE regimen had fewer moderate to severe reports in mobility, self-care, discomfort, anxiety, and depression than those who received sorafenib. Worsening health status contributed to a greater number of treatment discontinuation than disease progression. Investigators found that following discontinuation, more patients experienced moderate to extreme problems in all health-related quality of life domains. These results support the STRIDE regimen’s benefits to quality-of-life benefits, especially for patients who remain on treatment.
The HIMALAYA was a randomized, open-label, multicenter study. Investigators administered STRIDE therapy using a priming dose of 300 mg tremelimumab along with 1500 mg of durvalumab followed by regular durvalumab every 4 weeks. The trial consisted of 1324 patients with unresectable, advanced hepatocellular carcinoma who were not treated with prior systemic therapy and who were not eligible for locoregional therapy to the liver and surrounding tissue. The primary end point was OS for STRIDE vs sorafenib, and the secondary end points were OS for durvalumab monotherapy vs sorafenib, objective response rate, and progression free survival for STRIDE and durvalumab alone.
The primary results for HIMALAYA were presented earlier this year at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium in January. The results reported that the trial met its primary endpoint, showing substantial OS improvement associated with the STRIDE treatment regimen. The safety profiles of both STRIDE and durvalumab monotherapy were consistent with past 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 the 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 = .0035), and for durvalumab alone vs sorafenib it was 0.86 (95.67% CI, 0.73-1.03; noninferiority margin, 1.08).
Treatment-emergent adverse events of grade 3/4 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 across 16 countries, spanning the US, Canada, Europe, South America, and Asia.
1. AstraZeneca shares data at EASL and ESMO World GI for Imfinzi combinations in patients with liver and biliary tract cancers. Press release. AstraZeneca; July 1, 2022. Accessed July 6, 2022. https://bit.ly/3yJrTUv
2. Abou-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