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.ANN-LII CHENGEl-Khoueiry A.B.Abou-Alfa G.K.2021-08-312021-08-3120201078-0432https://www.scopus.com/inward/record.uri?eid=2-s2.0-85101032479&doi=10.1158%2f1078-0432.CCR-19-3884&partnerID=40&md5=434183b0aa293ffd44b138c49ec61599https://scholars.lib.ntu.edu.tw/handle/123456789/580018Purpose: 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]SDG3alpha 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 Adultjournal article10.1158/1078-0432.CCR-19-3884326363192-s2.0-85101032479