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Abstract Details
Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial
Robin Kate Kelley1, Baek-Yeol Ryoo2, Philippe Merle3, Joong-Won Park4, Luigi Bolondi5, Stephen L Chan6, Ho Yeong Lim7, Ari D Baron8, Francis Parnis9, Jennifer Knox10, Stéphane Cattan11, Thomas Yau12, Julie C Lougheed13, Steven Milwee14, Anthony B El-Khoueiry15, Ann-Lii Cheng16, Tim Meyer17, Ghassan K Abou-Alfa1819
Author information
1UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA katie.kelley@ucsf.edu.
2Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3Groupement Hospitalier Lyon Nord, Lyon, France.
4National Cancer Center, Goyang, Republic of Korea.
5Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
6Department of Clinical Oncology, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong.
7Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
8California Pacific Medical Center, San Francisco, California, USA.
9Adelaide Cancer Centre, Adelaide University, Kurralta Park, South Australia, Australia.
10Princess Margaret Hospital, Toronto, Ontario, Canada.
11CHRU Lille, Lille, France.
12Queen Mary Hospital, Hong Kong, China.
13Medical Affairs, Exelixis Inc, Alameda, California, USA.
14Clinical Development, Exelixis Inc, Alameda, California, USA.
15USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
16National Taiwan University Hospital, Taipei, Taiwan.
17Royal Free Hospital, London, UK.
18Memorial Sloan Kettering Cancer Center, New York, United States.
19Weill Medical College at Cornell University, New York, United States.
Abstract
Objective: In the phase 3 CELESTIAL trial, cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). This subgroup analysis evaluated cabozantinib in patients who had received sorafenib as the only prior systemic therapy.
Methods: CELESTIAL randomised (2:1) patients with advanced HCC and Child-Pugh class A liver function to treatment with cabozantinib (60 mg daily) or placebo. Eligibility required prior treatment with sorafenib, and patients could have received ≤2 prior systemic regimens. The primary endpoint was OS. Outcomes in patients who had received sorafenib as the only prior therapy were analysed by duration of prior sorafenib (<3 months, 3 to <6 months and ≥6 months).
Results: Of patients who had received only prior sorafenib, 331 were randomised to cabozantinib and 164 to placebo; 136 patients had received sorafenib for <3 months, 141 for 3 to <6 months and 217 for ≥6 months. Cabozantinib improved OS relative to placebo in the overall second-line population who had received only prior sorafenib (median 11.3 vs 7.2 months; HR=0.70, 95% CI 0.55 to 0.88). This improvement was maintained in analyses by prior sorafenib duration with longer duration generally corresponding to longer median OS-median OS 8.9 vs 6.9 months (HR=0.72, 95% CI 0.47 to 1.10) for prior sorafenib <3 months, 11.5 vs 6.5 months (HR=0.65, 95% CI 0.43 to 1.00) for 3 to <6 months and 12.3 vs 9.2 months (HR=0.82, 95% CI 0.58 to 1.16) for ≥6 months. Cabozantinib also improved PFS in all duration subgroups. Safety data were consistent with the overall study population.
Conclusion: Cabozantinib improved efficacy outcomes versus placebo in the second-line population who had received only prior sorafenib irrespective of duration of prior sorafenib treatment, further supporting the utility of cabozantinib in the evolving treatment landscape of HCC.