Impact of post-progression survival in second-line treatment with molecular target agents for unresectable hepatocellular carcinoma.

Abstract

Sequential therapies are essential to extend overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). Several second-line treatments with molecular target agents have shown survival benefits. However, the significance of post-progression survival (PPS) in extending OS in patients with HCC given such treatments remains uncertain. Through a systematic review of the literature in the PubMed database, this study investigated the correlation between PPS and OS and that between progression-free survival (PFS) and OS in patients with HCC given second-line treatments. In total, 3935 patients who had received second-line treatment with regorafenib, ramucirumab, or cabozantinib, which are approved molecular target agents, were identified. In the patients treated with regorafenib, PPS showed a strong correlation with OS (R2=0.729, R=0.854, p<0.001) whereas PFS showed a weak correlation (R2=0.218, R=0.467, p=0.021). In the patients treated with ramucirumab, PPS showed a strong correlation with OS (R2=0.800, R=0.894, p=0.016) whereas PFS showed a negligible correlation (R2=0.020, R=0.140, p=0.791). In the patients treated with cabozantinib, PPS showed a strong correlation with OS (R2=0.856, R=0.925, p=0.003) as did PFS (R2=0.946, R=0.973, p<0.001). PPS plays a more significant role than PFS in extending OS in patients given second-line treatment for unresectable HCC. Sequential therapies after disease progression in second-line treatment are essential to acquire good OS. Maintenance of hepatic reserve function and the patient's general condition is essential during systemic treatments for unresectable HCC.