Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial

ESMO Open

article

Thomas Yau¹  Julie C. Lougheed²  Steven Milwee³  Anthony B. El-Khoueiry⁴  Ann-Lii Cheng⁵  Tim Meyer⁶  Ghassan K. Abou-Alfa⁷  RobinKate Kelley⁹  Baek-Yeol Ryoo^1,10  Philippe. Merle^1,11  Joong-Won Park^1,12  Luigi Bolondi^1,13  Stephen L. Chan^1,14  HoYeong Lim^1,15  Ari D. Baron^1,16  Francis Parnis^1,17  Jennifer Knox^1,18  Stéphane Cattan^1,19 

[1] Queen Mary Hospital;Medical Affairs, Exelixis Inc;Clinical Development, Exelixis Inc;USC Norris Comprehensive Cancer Center;National Taiwan University Hospital;Royal Free Hospital;Memorial Sloan Kettering Cancer Center;Weill Medical College at Cornell University;UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco;Asan Medical Center, University of Ulsan College of Medicine;Groupement Hospitalier Lyon Nord;National Cancer Center;Department of Medical and Surgical Sciences, University of Bologna;Department of Clinical Oncology, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong;Samsung Medical Center, Sungkyunkwan University;California Pacific Medical Center;Adelaide Cancer Centre, Adelaide University;Princess Margaret Hospital;CHRU Lille

关键词: hepatocellular carcinoma;    tyrosine kinase inhibitor;    cabozantinib;    sorafenib;   

DOI  :  10.1136/esmoopen-2020-000714

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

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.Clinical trial number NCT01908426.

【 授权许可】

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