KEY TAKEAWAYS
- The phase 3 HIMALAYA Study aimed to evaluate the long-term OS benefit of the STRIDE regimen (tremelimumab+durvalumab) vs. sorafenib in uHCC patients.
- Participants with uHCC were randomized to receive tremelimumab+durvalumab), durvalumab monotherapy, or sorafenib.
- The study showed that the STRIDE regimen demonstrates a significant and durable long-term OS benefit vs. sorafenib, with estimated 36-month OS rates of 30.7% and 20.2%, respectively. The results confirm the sustained OS benefit of STRIDE, with unprecedented 3- and 4-year OS rates.
In the phase 3 HIMALAYA study, STRIDE (tremelimumab plus durvalumab) showed superior overall survival (OS) compared to sorafenib, while durvalumab monotherapy was noninferior to sorafenib in unresectable hepatocellular carcinoma (uHCC). After follow-up for 4 years, researchers reported (33 months) significant and durable long-term survival benefit vs. estimated 36-month OS rates of 30.7% versus 20.2% for sorafenib.
A total of 1171 Patients (pts) with uHCC and not treated previously were randomly given STRIDE(n=393), (tremelimumab 300 mg for one dose plus durvalumab 1500 mg every 4 weeks [Q4W]), durvalumab monotherapy (n=389)(1500 mg Q4W) or sorafenib (n=389) (400 mg twice daily). The study aimed to evaluate the OS for STRIDE vs sorafenib. The update analysis was on January 23, 2023 ((78% OS data maturity for STRIDE). The study also reported the OS and serious treatment-related adverse events (TRAEs). Cox proportional hazards model was used to calculate OS HRs (hazard ratio ) and confidence intervals (CIs). Additionally, baseline demographics and disease characteristics were examined in long-term survivors (LTS) who survived for ≥36 months after randomization. The median (95% CI) duration of OS for STRIDE was 49.12 months(46.95–50.17), for durvalumab monotherapy was 48.46 months(46.82–49.81), and for sorafenib was 47.31 months(45.08–49.15). The OS HRs for STRIDE vs. sorafenib 0.78 (0.67–0.92) and steady with primary analysis. The OS rates for STRIDE at 36 months (30.7%) and sorafenib (19.8%) were consistent with the primary analysis. The OS rate remained higher at 48 months for STRIDE (25.2%) than for sorafenib (15.1%). Severe TRAEs, including death, happened in 17.5% treated with STRIDE vs. 9.6% with sorafenib, with no new events observed after the primary analysis for STRIDE. Durvalumab demonstrated noninferiority to sorafenib in terms of OS and maintained a consistent safety profile. The baseline demographics and characteristics of long-term survivors in the STRIDE arm were similar to the overall analysis set, suggesting that the long-term survival benefit was not limited to specific participant subgroups. The study concluded that the data reaffirm the long-term benefit of STRIDE over sorafenib, with unprecedented 3- and 4-year OS rates and the longest follow-up in uHCC phase 3 studies. STRIDE maintains a tolerable safety profile without new serious events, supporting its benefits in a diverse uHCC population.
Source: https://www.annalsofoncology.org/article/S0923-7534(23)00629-4/fulltext
Clinical Trial : https://classic.clinicaltrials.gov/ct2/show/NCT03298451
B. Sangro S. Chan R. Kelley G. Lau M. Kudo W. Sukeepaisarnjaroen E. De Toni J. Furuse Y. Kang P. Galle L. Rimassa A. Heurgué V. Tam T. Dao S. Thungappa V. Breder Y. Ostapenko M. Reig M. Makowsky C. Gupta A. Negro G. Abou-Alfa Show less DOI:https://doi.org/10.1016/j.annonc.2023.04.487
