ESMO Asia 2025 | Emerging strategies for unresectable or advanced hepatocellular carcinoma

For patients with unresectable HCC or advanced HCC, we use in clinical practice different immunotherapy combinations. We have atezolizumab plus bevacizumab, we have durvalumab plus tremelimumab according to the STRIDE regimen, and we have nivolumab plus ipilimumab. Of course, we also have tyrosine kinase inhibitors for patients who are not suitable for immunotherapy. However, all these drugs or combinations, especially the immunotherapy combinations, have been tested in phase three trials, enrolling only patients with a very well-preserved liver function and in very good clinical conditions. And in the clinic every day, we see patients with different characteristics, maybe less well-preserved function, with comorbidities, with concomitant medications, not in so well clinical conditions, in not so good clinical conditions. So we need the data for these immunotherapy combinations in a broader patient population. And at ESMO Asia 2025, the safety results in Asian patients from the Phase 3B-SIERRA study were presented. And the Phase 3B-SIERRA study is a study that is testing the combination of Durvalumab plus Tremelimumab, according to the STRIDE regimen. So the regimen is still in the Phase III Himalaya study, but in patients who were excluded from the Himalaya trial for different baseline characteristics. In particular, in the SIERRA study, patients with either Child-Pugh B7 or B8 liver cirrhosis or ECOG performance status 2 or main portal vein thrombosis were included. And these are three groups of patients who were excluded from the Himalaya trial, the registration of the pivotal phase 3 trial. So patients for this group of patients, for these groups of patients, we don’t have data. The safety data of the overall population included in the SIERRA study were presented at ESMO this year. And at ESMO Asia 2025, the safety results in the Asian population were presented. And what is interesting here is that the primary endpoint of this trial is represented by possibly related adverse events of grade 3 and 4 and also response rate. And the adverse events presented at ESMO Asia 2025 are very similar to the adverse events in the overall population enrolled in the SIERRA study and also very similar to the adverse events observed in the Himalaya trial. So even if patients are in less good clinical conditions with less well-preserved liver function or with main portal vein thrombosis, the safety profile is quite similar. For instance, the use of steroids to manage the immune-mediated adverse events was very similar in this trial, in the SIERRA trial in patients from Asia, very similar to what we have observed in the Himalaya study. So overall, the phase 3B SIERRA study is testing safety and efficacy of STRIDE in first line in non-resectable HCC in a broader population with a poor prognosis compared to the Himalaya study. And the safety data in the 47 patients from Asia, so the data presented at ESMO Asia 2025, showed a safety profile that is manageable and very similar to the global population of the SIERRA study. The study is still ongoing, and so we will have to wait for more results, and the further results will be presented at further conferences, and then we will publish, and then in the near future we will have the results in the overall population and we will also have efficacy results to confirm the possibility to use this regimen in clinical practice in a broader patient population compared to the population that was enrolled in the Himalaya study.

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