Kelley RK, et al. - Researchers assessed clinical outcomes with cabozantinib (C), an inhibitor of MET, VEGFR, and AXL, in CELESTIAL (a phase III trial) based on AFP response or progression on treatment. In pts with previously treated advanced HCC, significantly improved overall survival (OS) and progression-free survival (PFS) were reported with C vs P in CELESTIAL. C (60 mg daily) or P were given to 707 pts, using randomization 2:1. Patients with a pathologic diagnosis of HCC, Child-Pugh score A, and ECOG PS ≤ 1 were eligible for inclusion. For HCC, prior sorafenib and ≤ 2 lines of prior systemic therapy were received by pts. For pts with baseline AFP ≥ 20 ng/mL, they assessed outcomes according to AFP response ( ≥ 20% decrease from baseline) or progression ( ≥ 20% increase from baseline) at Week 8. Baseline AFP ≥ 20 ng/mL was present in 331 pts (70%) in the C arm and 160 (68%) in the P arm. Of these pts, 236 (71%) and 111 (69%), respectively, were evaluable for AFP response at week 8. With C vs P, a higher AFP response rate was observed. For pts with previously treated advanced HCC, longer OS and PFS with C were observed in association with AFP response.