KEY TAKEAWAYS
- The study aimed to investigate the efficacy and safety of anlotinib combined with penpulimab compared to sorafenib as 1L therapy for aHCC.
- The primary endpoints were to determine PFS and OS.
- Researchers noticed that anlotinib + penpulimab significantly improves PFS and OS compared to sorafenib.
In this randomized, controlled, open-label, multicenter, phase III study; Jian Zhou and the team aimed to evaluate the efficacy and safety of anlotinib (VEGFR/PDGFR/FGFR/c-kit-TKI) combined with penpulimab (anti-PD-1 IgG1 monoclonal antibody) vs sorafenib as 1L therapy for advanced hepatocellular carcinoma (aHCC).
They performed an inclusive analysis involving eligible patients with aHCC, who were randomized in a 2:1 ratio to receive anlotinib (10 mg, orally, once daily on days 1-14) combined with penpulimab (200 mg, intravenously, every 3 weeks) or sorafenib (400 mg, orally, twice daily). Patients were stratified based on macrovascular invasion and/or extrahepatic metastases, baseline serum AFP levels (<400 vs. ≥400 ng/mL), and ECOG performance status (0 vs. 1).
The dual primary endpoints of the study were progression-free survival (PFS) and overall survival (OS), evaluated per RECIST v1.1 by independent review committee (IRC). Secondary endpoints included PFS, overall response rate (ORR), disease control rate (DCR), duration of response (DOR), and safety. The final analysis for PFS was conducted after 312 PFS events, while the planned interim analysis for OS occurred after 332 patient deaths.
About 649 patients were randomized (anlotinib + penpulimab, 433; sorafenib, 216). Demographic and baseline characteristics were generally balanced across treatment arms. Overall, 41% of patients had macrovascular invasion, and 62% had extrahepatic metastasis. At the final analysis for PFS (data cutoff: 5 June 2023), 313 PFS events had occurred.
The median PFS was significantly improved with anlotinib + penpulimab compared to sorafenib (6.9 months [95% CI 5.8-8.0] vs 2.8 months [2.7-4.1]; HR 0.53 [95% CI 0.41-0.68]); P<0.0001). At the interim analysis for OS (data cutoff: 29 January 2024), 338 OS events had occurred.
The median OS was significantly prolonged with anlotinib + penpulimab compared to sorafenib (16.5 months [95% CI 14.7-19.7] vs 13.2 months [95% CI 9.7-16.9]; HR 0.69 [95% CI 0.52-0.92]; P=0.0013). The incidence rates of grade ≥3 treatment-related adverse events (TRAEs) were 48.2% in the anlotinib + penpulimab arm and 47.4% in the sorafenib arm.
Adverse events leading to dose modification (16.2% vs 29.9%) were lower with anlotinib + penpulimab compared with sorafenib. The incidence of any grade immune-mediated adverse events was lower in patients treated with anlotinib + penpulimab: pneumonitis (2.5%), colitis (0.9%), and hepatitis (0.5%).
The study concluded that the combination of anlotinib and penpulimab significantly prolonged PFS and OS compared to sorafenib, with no new safety signals observed, thereby establishing it as a promising first-line treatment option for aHCC.
The trial was sponsored by the Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/26
Clinical Trial: https://clinicaltrials.gov/study/NCT04344158
Zhou J, Fan J, Jiao S.C, et al. (2024). “Primary results from the phase III ALTN-AK105-III-02 study: Anlotinib plus penpulimab versus sorafenib as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC).” Presented at ESMO 2024 (Abstract LBA40).
