EVOLVE-1: Phase 3 study of everolimus for advanced HCC that progressed during or after sorafenib

Autor:	Jean-Frédéric Blanc, Eric Assenat, Andrew X. Zhu, Li-Tzong Chen, Bruno Daniele, Ho Yeong Lim, Annette Jappe, Chao-Long Chen, Etienne Dorval, Dalila Sellami, Kevin Perraud, Junji Furuse, Arndt Vogel, Markus Peck-Radosavljevic, Stéphane Cattan, Yoon-Koo Kang, Özlem Anak, Ronnie T.P. Poon, Masatoshi Kudo, Armando Santoro
Rok vydání:	2014
Předmět:	Oncology Sorafenib Cancer Research medicine.medical_specialty Everolimus Randomization business.industry Phases of clinical research Placebo BCLC Stage Surgery Internal medicine Clinical endpoint Medicine Liver function business medicine.drug
Zdroj:	Journal of Clinical Oncology. 32:172-172
ISSN:	1527-7755 0732-183X
DOI:	10.1200/jco.2014.32.3_suppl.172
Popis:	172 Background: No effective treatment options exist for advanced HCC following sorafenib failure. Preliminary data suggest everolimus may provide benefit after sorafenib. EVOLVE-1 (NCT01035229) assessed the efficacy and safety of everolimus for advanced HCC after sorafenib failure. Methods: Pts aged ≥18 y with BCLC stage B or C HCC and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were sorafenib intolerant were randomized 2:1 to everolimus 7.5 mg/d or placebo. All pts received best supportive care. Randomization was stratified by region (Asia v rest of world) and macrovascular invasion (yes v no). Study drug was given continuously until disease progression or intolerable toxicity. CT/MRI was performed every 6 wk. Primary endpoint was OS. Secondary endpoints were TTP, disease control rate (DCR; percentage of pts with best overall response of CR, PR, or SD per RECIST 1.0), and safety. Final analysis was performed when 454 deaths occurred. Results: 546 pts from 18 countries enrolled from Apr 2010 to Mar 2012 (everolimus = 362, placebo = 184). Baseline characteristics were balanced between arms; median age was 66.0 y, 84.8% of pts were male, 86.3% had BCLC stage C disease, 16.7% were from Asia, 32.8% had macrovascular invasion, and 74.0% had extrahepatic disease. Prior sorafenib was discontinued for disease progression in 80.8% of pts and intolerance in 19.0%. Median OS was 7.56 mo with everolimus and 7.33 mo with placebo (HR 1.05; 95% CI 0.86-1.27; P = .675). Median TTP was 2.96 mo and 2.60 mo, respectively (HR 0.93; 95% CI 0.75-1.15). DCR was 56.1% and 45.1%, respectively (P = .010). The most common grade 3/4 AEs with everolimus (v placebo) were anemia (7.8% v 3.3%), asthenia (7.8% v 5.5%), decreased appetite (6.1% v 0.5%), and hepatitis B viral load increase or reappearance (6.1% v 4.4%). No pts experienced HCV flare. HBV reactivation was experienced by 39 pts (29 everolimus, 10 placebo); all cases were asymptomatic, but 3 everolimus recipients discontinued therapy. Conclusions: Everolimus did not improve OS in pts with advanced HCC whose disease progressed on or after sorafenib or who were sorafenib intolerant. The safety profile was consistent with that previously observed with everolimus. Clinical trial information: NCT01035229.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::3fd3a119527e4017b0e849f92be1d0d8 https://doi.org/10.1200/jco.2014.32.3_suppl.172 Zobrazit plný text záznamu