American Association for Cancer Research
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Supp Figure S3 from Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma

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posted on 2023-03-31, 21:49 authored by Robin Kate Kelley, Tim Meyer, Lorenza Rimassa, Philippe Merle, Joong-Won Park, Thomas Yau, Stephen L. Chan, Jean-Frederic Blanc, Vincent C. Tam, Albert Tran, Vincenzo Dadduzio, David W. Markby, Rajesh Kaldate, Ann-Lii Cheng, Anthony B. El-Khoueiry, Ghassan K. Abou-Alfa

Figure S3. AFP response cutoff determination for overall survival by maximally selected rank statistics. Cutpoint determination plots showing (A) histogram distribution and (B) rank statistic plot of percent AFP change from baseline at Week 8 for patients in the cabozantinib group with baseline AFP {greater than or equal to}20 ng/mL. *Calculated value of 0.48%, rounded to 0% for all subsequent analyses.



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. 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. 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. 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.