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Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma

Kelley, RK; Meyer, T; Rimassa, L; Merle, P; Park, J-W; Yau, T; Chan, SL; ... Abou-Alfa, GK; + view all (2020) Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma. Clinical Cancer Research , 26 (18) pp. 4795-4804. 10.1158/1078-0432.CCR-19-3884. Green open access

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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.

Type: Article
Title: Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/1078-0432.CCR-19-3884
Publisher version: https://doi.org/10.1158/1078-0432.CCR-19-3884
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10112537
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