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Abstract Details
Serum alpha-fetoprotein levels and clinical outcome in the phase 3 CELESTIAL study of cabozantinib versus placebo in patients with advanced hepatocellular carcinoma
Clin Cancer Res. 2020 Jul 7;clincanres.3884.2019. doi: 10.1158/1078-0432.CCR-19-3884.Online ahead of print.
Robin K Kelley1, Tim Meyer2, Lorenza Rimassa3, Philippe Merle4, Joong-Won Park5, Thomas Yau6, Stephen L Chan7, Jean-Frederic Blanc8, Vincent C Tam9, Albert Tran10, Vincenzo Dadduzio11, David W Markby12, Rajesh Kaldate13, Ann-Lii Cheng14, Anthony B El-Khoueiry15, Ghassan K Abou-Alfa16
Author information
1Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco katie.kelley@ucsf.edu.
2UCL Cancer Institute, University College London.
3Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center - IRCCS; Department of Biomedical Sciences, Humanitas University.
4Groupement Hospitalier Lyon Nord, Service d'Hépatologie, Hospices Civils de Lyon.
5Center for Liver Cancer, National Cancer Center, Goyang-si, Republic of Korea.
6Queen Mary Hospital.
7Clinical Oncology, Chinese University of Hong Kong, State Key Laboratory of South China.
8Hepato-Gastroenterology and Digestive Oncology, University Hospital Of Bordeaux.
91331 29th Street NW, Tom Baker Cancer Centre, University of Calgary.
10Groupe Hospitalier L'Archet.
11Department of Oncology, Veneto Institute of Oncology IOV - IRCCS.
12Medical Affairs, Exelixis, Inc.
13Exelixis, Inc.
14Graduate Institute of Oncology, National Taiwan University.
15Division of Medical Oncology, USC Norris Comprehensive Cancer Center.
16Gastrointestinal Oncology Service, Dept. of Medicine, Memorial Sloan Kettering Cancer Center.
Abstract
Purpose The phase 3 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. Experimental design 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% 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.