The combination of tremelimumab plus durvalumab improved survival for patients with unresectable hepatocellular carcinoma in the phase 3 HIMALAYA trial.
CancerNetwork® spoke with Ghassan K. Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Comprehensive Cancer Center, at the 2022 Gastrointestinal Cancer Symposium about the key results and main takeaways to emerge in patients with hepatocellular carcinoma (HCC) who were treated with tremelimumab at 300 mg plus durvalumab (Imfinzi), tremelimumab at 75 mg plus durvalumab, or durvalumab alone vs sorafenib (Nexavar) in the phase 3 HIMALAYA study (NCT03298451).
In the HIMALAYA study, the primary end point was positive showing improved [median overall] survival for the tremelimumab [at a] single dose of 300 mg plus durvalumab of 16.4 months compared with 13.8 for sorafenib, with a hazard ratio of 0.78 [95% CI, 96% CI, 0.65-0.92; P = .0035], which is clinically and statistically significant. If anything, the separation of the curve was noticeable around 4 months and started propagating further enough that when we did a landmark evaluation at 9 months, we have seen the hazard ratio improve markedly up to 0.70. That suppression continued at [follow-up] analysis at 18 months, 24 months, and 36 months, enough that by 3 years, 30% of the were still alive with the tremelimumab single dose plus durvalumab.
Now, this brings up an important question in regard to the priming effect that’s needed for [efficacy]. Interestingly, that’s why the PFS [progression-free survival] was totally equal between the 2 arms of tremelimumab single dose plus durvalumab, single-agent durvalumab, and sorafenib. There was no difference at all even though the separation started to be seen afterwards. More importantly, the critical point is that the priming of the T cells happened right away. The time to response was only 2 months for tremelimumab plus durvalumab and close to 5 months for sorafenib. If anything, it tells us one more time that we have been using new science and the new language of checkpoint inhibitors, but we’re still using the old dictionary of median survival and median PFS. I would say here the PFS is not of critical importance. If anything, the improvement in survival is the key player that we have seen not only with HCC but with other diseases such as melanoma, lung cancer, gastric cancer, etc.
Abou-Alfa G, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA. J Clin Oncol. 2022;40(suppl 4):379. doi: 10.1200/JCO.2022.40.4_suppl.379