Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma
Journal
Clinical Cancer Research
Journal Volume
26
Journal Issue
18
Pages
4795-4804
Date Issued
2020
Author(s)
Kelley R.K.
Meyer T.
Rimassa L.
Merle P.
Park J.-W.
Yau T.
Chan S.L.
Blanc J.-F.
Tam V.C.
Tran A.
Dadduzio V.
Markby D.W.
Kaldate R.
El-Khoueiry A.B.
Abou-Alfa G.K.
Abstract
Purpose: The phase III CELESTIAL study demonstrated improved overall survival (OS) and progression-free survival (PFS) with cabozantinib versus placebo in patients with previously treated, advanced hepatocellular carcinoma (HCC). We analyzed outcomes by baseline alpha-fetoprotein (AFP) and on-treatment AFP changes. Patients and Methods: Serum AFP was measured every 8 weeks by blinded, centralized testing. Outcomes were analyzed by baseline AFP bifurcated at 400 ng/mL and by on-treatment AFP response (?20% decrease from baseline at Week 8). The optimal cutoff for change in AFP at Week 8 was evaluated using maximally selected rank statistics. Results: Median OS for cabozantinib versus placebo was 13.9 versus 10.3 months [HR, 0.81; 95% confidence interval (CI), 0.62-1.04] for patients with baseline AFP <400 ng/mL, and 8.5 versus 5.2 months (HR, 0.71; 95% CI, 0.54-0.94) for patients with baseline AFP ?400 ng/mL. Week 8 AFP response rate was 50% for cabozantinib versus 13% for placebo. In the cabozantinib arm, median OS for patients with and without AFP response was 16.1 versus 9.1 months (HR, 0.61; 95% CI, 0.45-0.84). AFP response was independently associated with longer OS. The optimal cutoff for association with OS in the cabozantinib arm was ?0% change in AFP at Week 8 [AFP control; HR 0.50 (95% CI, 0.35-0.71)]. HRs for PFS were consistent with those for OS. Conclusions: Cabozantinib improved outcomes versus placebo across a range of baseline AFP levels. On-treatment AFP response and control rates were higher with cabozantinib than placebo, and were associated with longer OS and PFS with cabozantinib. ? 2020 American Association for Cancer Research.
SDGs
Other Subjects
alpha fetoprotein; cabozantinib; placebo; sorafenib; AFP protein, human; alpha fetoprotein; anilide; cabozantinib; placebo; protein kinase inhibitor; pyridine derivative; adult; advanced cancer; aged; Article; cancer control; clinical outcome; controlled study; drug efficacy; drug safety; drug withdrawal; exploratory research; female; human; liver cell carcinoma; major clinical study; male; outcome assessment; overall survival; phase 3 clinical trial; progression free survival; protein analysis; protein blood level; randomized controlled trial; reference value; survival time; treatment duration; treatment response; unspecified side effect; blood; cancer staging; clinical trial; liver cell carcinoma; liver tumor; middle aged; mortality; prognosis; very elderly; young adult; Adult; Aged; Aged, 80 and over; alpha-Fetoproteins; Anilides; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Placebos; Prognosis; Progression-Free Survival; Protein Kinase Inhibitors; Pyridines; Reference Values; Young Adult
Publisher
American Association for Cancer Research Inc.
Type
journal article