Long-Term OS Benefit of STRIDE Regimen Among Patients With Unresectable Hepatocellular Carcinoma

4-Year Follow-Up Analysis From the Phase 3 HIMALYA Study

At the 2023 World Congress on Gastrointestinal Cancers, Bruno Sangro, MD, PhD, University of Navarra, Pamplona, Spain, discusses updated long-term overall survival results from the phase 3 HIMALYA study.

Dr Sangro concluded this analysis “shows that STRIDE provides superior survival compared to sorafenib, and it does so irrespective of baseline characteristics including etiology and occurs irrespective of response with patients achieving disease control, achieving also long-term survival.”

Transcript:

My name is Bruno Sangro, I work in the University of Navarra in Pamplona in Spain, and I have presented at this meeting a 4-year updated survival analysis of the HIMALAYA trial, a trial of durvalumab and tremelimumab for patients with unresectable HCC.

The design of this trial is easy. Patients were randomized 1-to-1-to-1 to STRIDE, which is a single high dose of tremelimumab and durvalumab, durvalumab monotherapy, or sorafenib, with the intention to prove the superiority of STRIDE versus sorafenib as the primary end point. But there were other important end points, including the long-term survival in the pre-planned analysis.

The primary analysis showed the superiority of STRIDE versus sorafenib, and in this updated analysis that we have presented, there were 3 important messages. One, was the hazard ratio remained consistent with that of the primary analysis. Second, the difference in the survival rates were increased over time. At 18 months, patients survived on STRIDE 17% more than with sorafenib. At 4 years, the difference is 67%. In the end, there is results in an unprecedented 4-year survival data with 1 in 4 patients alive at 4 years. We have also characterized the profile of the long-term survivors, defined as patients who survived for 3 years or more, and interestingly, we have seen that patients that were long-term survivors with STRIDE had similar baseline characteristics in terms of tumor burden, or viral etiology, or others than the intention-to-treat population. In other words, what we found is that there was no specific subgroup of patients that were striving these improved survival benefit. That includes patients who, upon discontinuation of the primary treatment, received an additional or more anti-cancer therapies.

We also have performed a specific analysis of the best overall response and the impact on survival. Checkpoint inhibitors sometimes induce deep and durable responses, and one may be tempted to believe that only responders may benefit from therapy. Contrary to that, we have observed that the populations of long-term survivors with STRIDE was inclusive of patients with complete responses, partial responses, but also stable diseases. A significant proportion of patients with long-term survival were indeed patients with stable disease. Most of the patients that were long-term survivors, indeed had disease control as the best overall response.

Now, if you analyze survival based on whether the patients achieved disease control or not, what we observed, and this is so important for clinical practice, is that patients who achieved disease control with STRIDE survived much better than patients who achieved disease control with sorafenib. At 4 years, 1 in 3 patients who achieved disease control with STRIDE were alive compared to 1 in 5 patients who achieved disease control with sorafenib, an important result. And this with no new signals in terms of safety, there were no new serious treatment related adverse events after the primary analysis.

Altogether, the updated 4-year survival analysis shows that STRIDE provides superior survival compared to sorafenib, and it does so irrespective of baseline characteristics including etiology and occurs irrespective of response with patients achieving disease control, achieving also long-term survival. Altogether, this is illustrated by the fact that the updated analysis has shown these unprecedented 3- and 4-year survival data with 1 in 4 patients alive at 4 years, something we haven't seen up to now with any systemic treatment of [hepatocellular carcinoma]. And this sets STRIDE as an excellent first line option for the treatment of this patient population. Thank you very much for watching.

Source:

Sangro B, Chan S, Kelley R, et al. Four-year overall survival update from the phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-15