Adverse Events in Targeted Therapy for Unresectable Hepatocellular Carcinoma Predict Clinical Outcomes

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 <i>p</i> 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 (<i>p</i> for trend 0.037), 1.057-1.691-3.364 (<i>p</i> for trend 0.004), 1.176-0.686-0.281 (<i>p</i> for trend 0.002), 0.639-0.759-1.820 (<i>p</i> for trend 0.462), 1.030-0.959-0.147 (<i>p</i> for trend 0.011), and 0.697-0.609 (<i>p</i> for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592-1.073-2.811 (<i>p</i> for trend 0.255), 1.161-1.282-4.324 (<i>p</i> for trend 0.03), 0.965-0.781-0.655 (<i>p</i> for trend 0.095), 0.737-0.623-2.147 (<i>p</i> for trend 0.153), 1.061-0.832-0.800 (<i>p</i> for trend 0.391), and 1.412-0.560 (<i>p</i> for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects.