In a Chinese phase III trial (APOLLO) reported in The Lancet Oncology, Zhou et al evaluated whether the combination of the multikinase inhibitor anlotinib and the PD-1 inhibitor penpulimab improved progression-free survival and overall survival vs sorafenib in first-line treatment of unresectable hepatocellular carcinoma.
Study Details
In the multicenter open-label trial, 649 patients were randomly assigned 2:1 between August 2020 and June 2023 to receive anlotinib at 10 mg once daily on days 1 to 14 plus penpulimab at 200 mg on day 1 (n = 433) or sorafenib at 400 mg twice daily (n = 216) every 3 weeks. Treatment continued until disease progression or unacceptable toxicity. The co-primary endpoints were progression-free survival on masked independent review committee assessment and overall survival; the second interim analysis of overall survival is reported herein.
Key Findings
In the final progression-free survival analysis, median follow-up was 6.2 months in the anlotinib/penpulimab group and 4.2 months in the sorafenib group. Median progression-free survival was 6.9 months (95% confidence interval [CI] = 5.8–8.0 months) in the anlotinib/penpulimab group vs 2.8 months (95% CI = 2.7–4.1 months) in the sorafenib group (hazard ratio [HR] = 0.52, 95% CI = 0.41–0.66, P < .0001). Subsequent systemic anticancer therapy was received by 37% of the anlotinib/penpulimab group and 44% of the sorafenib group, most commonly targeted therapy (23% vs 26%) and PD-1/-L1 inhibitors (13% vs 21%).
For the second interim analysis of overall survival, median follow-up times were 15.3 months and 14.5 months, respectively. Median overall survival was 16.5 months (95% CI = 14.7–19.0 months) in the anlotinib/penpulimab group vs 13.2 months (95% CI = 9.7–16.9 months) in the sorafenib group (HR = 0.69, 95% CI = 0.55–0.87, P = .0014).
Treatment-related grade ≥ 3 adverse events occurred in 50% of the anlotinib/penpulimab group and 47% of the sorafenib group; the most common adverse events were hypertension (17% vs 10%) and decreased platelets (9% vs 6%). Treatment-related serious adverse events were reported in 21% vs 9% of patients. Treatment-related death occurred in one patient in the anlotinib/penpulimab group (due to upper gastrointestinal hemorrhage) and in two patients in the sorafenib group (due to hepatic failure and death of unknown cause).
The investigators concluded: “Anlotinib plus penpulimab significantly improved progression-free survival and overall survival vs sorafenib in unresectable [hepatocellular carcinoma] and might be a new first-line option. These findings require verification in other regions of the world.”
Jia Fan, MD, of the Department of Hepatobiliary Surgery and Liver Transplantation, Zhongshan Hospital, Fudan University, Shanghai, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Chia Tai Tianqing Pharmaceutical Group. For full disclosures of all study authors, visit The Lancet Oncology.
