Dr. Li on the Potential For First-Line Triplet Therapy in HCC

Daneng Li, MD, associate professor, Department of Medical Oncology & Therapeutics Research, co-director, Neuroendocrine Tumor Program, City of Hope, discusses the investigation of triplet combination therapy for patients with hepatocellular carcinoma (HCC) in the phase 1/2 Morpheus-Liver study (NCT04524871).

The utilization of doublet therapies has improved overall survival (OS), disease control, and quality of life in this patient population, Li begins. Notably, the current focus of research is now shifting to enhancing treatment responses and outcomes for more patients with this disease using triplet therapy, Li says.

The open-label, multicenter, randomized umbrella study evaluated the addition of tiragolumab to standard atezolizumab (Tecentriq) and bevacizumab (Avastin) and if it could improve outcomes in patients with advanced liver cancers, Li details. Patients were required to have locally advanced or metastatic unresectable HCC, and must not have been amenable to locoregional or curative therapy.

In this study, the triplet regimen increased objective response rates (ORR) and prolonged progression-free survival vs a standard atezolizumab/bevacizumab doublet, Li reports. Patients in the tiragolumab arm experienced an ORR of 42.5% vs 1.1% in the control arm. The median PFS was 11.1 months with the triplet compared with 4.2 months with the doublet regimen. Notably, no new safety signals were identified.

These findings indicate that tiragolumab plus atezolizumab and bevacizumab (Avastin) may provide an effective first-line treatment alternative for patients with unresectable HCC, Li states. Results from the Morpheus-Liver study also support the planned phase 3 IMbrave152/ SKYSCRAPER-14 (NCT05904886) trial investigating atezolizumab plus bevacizumab with tiragolumab vs atezolizumab plus bevacizumab, Li adds. This forthecoming pivotal trial will confirm whether triplet therapy can be established as the new standard of care for HCC patients, Li explains.

Ultimately, the Morpheus-Liver study represents a promising step forward in the treatment landscape for hepatocellular carcinoma (HCC), laying the groundwork for future investigations of triplet therapy in the first line, Li concludes.