Abstract
To assess the impact of adverse event (AE) severity, caused by targeted therapy, on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), a total of 183 patients with HCC treated with atezolizumab plus bevacizumab (40), lenvatinib (57), sorafenib (79), cabozantinib (3), ramucirumab (3), and regorafenib (1) were included in this study. Age-, AFP-, and ALBI score-adjusted hazard ratios (HRs) of AE grades 1 to 3 versus grade 0 for OS and PFS were calculated using Cox proportional hazards models. The linear trend of the HRs was assessed by calculating the p values for this trend. The most common AEs were appetite loss (AE grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). The adjusted HRs for OS of these AEs were 0.532-1.450-2.361 (p for trend 0.037), 1.057-1.691-3.364 (p for trend 0.004), 1.176-0.686-0.281 (p for trend 0.002), 0.639-0.759-1.820 (p for trend 0.462), 1.030-0.959-0.147 (p for trend 0.011), and 0.697-0.609 (p for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592-1.073-2.811 (p for trend 0.255), 1.161-1.282-4.324 (p for trend 0.03), 0.965-0.781-0.655 (p for trend 0.095), 0.737-0.623-2.147 (p for trend 0.153), 1.061-0.832-0.800 (p for trend 0.391), and 1.412-0.560 (p for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects.