Combination prolongs PFS in intermediate-stage hepatocellular carcinoma
Click Here to Manage Email Alerts
The addition of lenvatinib and pembrolizumab to transarterial chemoembolization extended PFS for patients with intermediate-stage hepatocellular carcinoma, according to randomized phase 3 study results.
Researchers who presented findings at ESMO Congress observed what they described as “an early trend” toward improved OS with the experimental regimen.
Transarterial chemoembolization is standard for patients with intermediate-stage hepatocellular carcinoma.
In prior studies, pembrolizumab (Keytruda, Merck), a PD-1 inhibitor, and lenvatinib (Lenvima, Eisai), a multikinase inhibitor, exhibited efficacy and appeared safe in hepatocellular carcinoma.
Josep Llovet, MD, PhD, director of the liver cancer program and professor of medicine at Icahn School of Medicine at Mount Sinai, and colleagues conducted the multicenter, double-blinded LEAP-012 study to assess whether the addition of both agents to transarterial chemoembolization would enhance clinical benefit for patients with intermediate-stage hepatocellular carcinoma.
The analysis included 480 patients with hepatocellular carcinoma not amenable to curative treatment. All patients had Child-Pugh class A disease, ECOG performance status of 0 or 1, and no portal vein invasion.
Researchers assigned 237 of them to lenvatinib — dosed at 12 mg or 8 mg daily based on body weight — and 400 mg pembrolizumab via IV every 6 weeks, plus transarterial chemoembolization. Transarterial chemoembolization took place 2 to 4 weeks after start of systemic therapy, with a maximum two treatments per tumor — for a maximum four — no more than once monthly. Lenvatinib continued until disease progression or discontinuation, and pembrolizumab continued for up to 2 years.
The other 243 patients received placebo plus transarterial chemoembolization.
PFS assessed by blinded independent central review and OS served as primary endpoints.
Median follow-up was 25.6 months (range, 12.6-43.5).
The trial met its primary endpoint, showing a statistically significant improvement in median PFS with the combination (14.6 months vs. 10 months; HR = 0.66; 95% CI, 0.51-0.84).
OS data remained immature at data cutoff. Early results favored the combination regimen (HR = 0.8; 95% CI, 0.57-1.11), but the difference had not reached statistical significance.
Investigators plan to conduct further OS analyses.
Lenvatinib and pembrolizumab exhibited safety profiles consistent with those observed in prior studies, according to Llovet and colleagues.
More than twice as many patients assigned lenvatinib and pembrolizumab developed grade 3 to grade 5 treatment-related adverse events (71.3% vs. 31.5%). A higher percentage of patients assigned the combination experienced treatment-related adverse events that led to discontinuation of treatment (8.4% vs. 1.2%).
Collapse
Llovet JM, et al. Abstract LBA3. Presented at: European Society for Medical Oncology Congress; Sept. 13-17; Barcelona, Spain.
Click Here to Manage Email Alerts