Ciro Celsa1,2, Giuseppe Cabibbo1, Marco Enea3, Salvatore Battaglia4, Giacomo E M Rizzo1, Anita Busacca1, Paolo Giuffrida1, Caterina Stornello1, Giuseppe Brancatelli5, Roberto Cannella3,5, Salvatore Gruttadauria6,7, Calogero Cammà1. 1. Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy. 2. Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, Italy. 3. Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy. 4. Dipartimento di Scienze Economiche, Aziendali e Statistiche, University of Palermo, Palermo, Italy. 5. Dipartimento di Biomedicina, Neuroscienze e Diagnostica avanzata (BIND), University of Palermo, Palermo, Italy. 6. Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center), Palermo, Italy. 7. Department of Surgery, University of Catania, Italy.
Abstract
BACKGROUND& AIMS: Time to progression (TTP) and progression-free survival (PFS) are commonly used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of TTP and PFS with overall survival (OS) in studies of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (u-HCC) by innovative methods. METHODS: A search of databases for studies of TACE for u-HCC reporting both OS and TTP or PFS was performed. Individual patient data were extracted from TTP/PFS and OS Kaplan-Meier curves of TACE arms. Pooled median TTP and OS were obtained from random-effect model. The surrogate relationships of hazard ratios (HRs) and median TTP for OS were evaluated by the coefficient of determination R2 . RESULTS: We identified 13 studies comparing TACE vs systemic therapy or vs TACE plus systemic therapy and including 1932 TACE-treated patients. Pooled median OS was 11.2 months (95% confidence interval [95%CI] 7.9-17.8), and pooled median TTP was 5.4 months (95%CI 3.8-8.0). Heterogeneity among studies was highly significant for both outcomes. The correlation between HR TTP and HR OS was moderate (R2 = 0.65. 95%CI 0.08-0.81). R2 value was 0.04 (95%CI 0.00-0.35) between median TTP and median OS. CONCLUSION: In studies of TACE for u-HCC, the surrogate relationship of radiology-based endpoints with OS is moderate. Multiple endpoints including hepatic decompensation, macrovascular invasion and extrahepatic spread are needed for future trials comparing systemic therapies or combination of TACE with systemic therapies vs TACE alone.
BACKGROUND& AIMS: Time to progression (TTP) and progression-free survival (PFS) are commonly used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of TTP and PFS with overall survival (OS) in studies of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (u-HCC) by innovative methods. METHODS: A search of databases for studies of TACE for u-HCC reporting both OS and TTP or PFS was performed. Individual patient data were extracted from TTP/PFS and OS Kaplan-Meier curves of TACE arms. Pooled median TTP and OS were obtained from random-effect model. The surrogate relationships of hazard ratios (HRs) and median TTP for OS were evaluated by the coefficient of determination R2 . RESULTS: We identified 13 studies comparing TACE vs systemic therapy or vs TACE plus systemic therapy and including 1932 TACE-treated patients. Pooled median OS was 11.2 months (95% confidence interval [95%CI] 7.9-17.8), and pooled median TTP was 5.4 months (95%CI 3.8-8.0). Heterogeneity among studies was highly significant for both outcomes. The correlation between HR TTP and HR OS was moderate (R2 = 0.65. 95%CI 0.08-0.81). R2 value was 0.04 (95%CI 0.00-0.35) between median TTP and median OS. CONCLUSION: In studies of TACE for u-HCC, the surrogate relationship of radiology-based endpoints with OS is moderate. Multiple endpoints including hepatic decompensation, macrovascular invasion and extrahepatic spread are needed for future trials comparing systemic therapies or combination of TACE with systemic therapies vs TACE alone.
Authors: Giuseppe Cabibbo; Maria Reig; Ciro Celsa; Ferran Torres; Salvatore Battaglia; Marco Enea; Giacomo Emanuele Maria Rizzo; Salvatore Petta; Vincenza Calvaruso; Vito Di Marco; Antonio Craxì; Amit G Singal; Jordi Bruix; Calogero Cammà Journal: Liver Cancer Date: 2021-11-23 Impact factor: 11.740