New option for first-line treatment
In his discussion of the abstract, Dr. El-Khoueiry raised a few issues with the HIMALAYA trial that he felt needed further investigation.
Due to the study design, no conclusions can be drawn regarding the STRIDE regimen versus durvalumab as a single agent – the study was not powered for that, he said.
Also, the trial excluded patients with main portal vein thrombosis (PVT), he noted, and he felt that the subgroup analysis of hepatitis C patients requires further study.
“Another point is that, compared with other studies, bleeding events were less common in the HIMALAYA trial, but it did exclude patients with main PVT who are at highest risk of bleeding,” he pointed out.
STRIDE has a different toxicity profile from that seen with VEGF-containing combinations (for example, containing bevacizumab) and has a lower bleeding risk and a manageable rate of immune-mediated adverse events that require steroids. “But looking at non-VEGF regimens, is there an advantage to this, since most subsequent therapies target VEGF?” he questioned.
Another question is if there is a role for single agent PD-1/PD-L1 in first-line HCC. “This trial found that durvalumab was noninferior to sorafenib. This could be a first-line treatment option for select patients – maybe those who are poor candidates for combination therapy or have contraindications to VEGF,” said Dr. El-Khoueiry.
Nevertheless, STRIDE represents an emerging treatment option for this population, especially for patients who have contraindications for bevacizumab and a high bleeding risk, he concluded.
“So for HCC, it is amazing that we now have multiple first-line treatment options available,” he said. “The choice of therapy should be guided by toxicity profile and patient specific contraindications.”
For the future, he emphasized that biomarker development is critical to enhance a personalized approach driven by tumor and host biology.
“Sorafenib is no longer an appropriate control arm for first-line trials,” he said. “Timing of transition from liver-directed therapy to systemic therapy is critical given multiple available options.”
HCC in the setting of compromised liver function continues to be an unmet need. “And finally, in the second line and beyond, therapy after first-line immunotherapy combinations is largely empiric,” he said. “Research is needed to establish the efficacy of available and future therapeutic options post immunotherapy and the optimal sequence.”
This study received funding from AstraZeneca, maker of durvalumab. Dr. Abou-Alfa and Dr. El-Khoueiry reported relationships with numerous pharmaceutical companies.
A version of this article first appeared on Medscape.com.