Dr El-Khoueiry on Regorafenib/Pembrolizumab in Advanced HCC After Prior Anti–PD-1/L1 Therapy

Anthony B. El-Khoueiry, MD, associate director, clinical research, University of Southern California (USC) Norris Comprehensive Cancer Center, associate professor, clinical medicine, the Keck School of Medicine of USC, discusses findings from a phase 2 trial (NCT04696055) evaluating regorafenib (Stivarga) plus pembrolizumab (Keytruda) in patients with advanced hepatocellular carcinoma (HCC) whose disease progressed on 1 prior immune checkpoint inhibitor–containing regimen.

Cohort 1 included patients who received prior treatment with atezolizumab (Tecentriq) plus bevacizumab (Avastin), and cohort 2 featured patients who were given any other immune-checkpoint inhibitor–based regimen, either as a single agent or as part of a combination. Patients in both cohorts received 90 mg of oral regorafenib per day for 3 weeks on and 1 week off plus 400 mg of intravenous pembrolizumab once every 6 weeks.

Regarding the trial’s primary end point of overall response rate (ORR), the ORR in cohort 1 (n = 68) was 5.9% (95% CI, 1.6%-14.4%) with a disease control rate (DCR) of 54.4% (95% CI, 41.9%-66.5%). In Cohort 2 (n = 27), the ORR was 11.1% (95% CI, 2.4%-29.2%) with a DCR of 74.1% (95% CI, 53.7%-88.9%). Notably, the study fell short of reaching its primary end point, as investigators anticipated an ORR of at least 35% to demonstrate superiority over the historical ORR of 20% in this setting, El-Khoueiry says.

El-Khoueiry notes that although patients in cohort 2 appeared to have better outcomes, this could be attributed to the more favorable disease characteristics of the patients in this group, including more patients with an ECOG performance status of 0 and Barcelona clinic liver cancer stage B disease, and fewer instances of macrovascular invasion or extrahepatic spread. El-Khoueiry explains that the study was not designed for a direct comparison between the cohorts.

Regarding the exploratory end point of progression-free survival (PFS), the median PFS was 2.8 months (95% CI, 2.4-3.9) in cohort 1 and 4.2 months (95% CI, 2.9-6.8) in cohort 2. The median overall survival was not evaluable in either cohort.