Early Decision Making in a Randomized Phase II Trial of Atezolizumab in Biliary Tract Cancer Using a Tumor Growth Inhibition-Survival Modeling Framework.
Clin Pharmacol Ther
; 114(3): 644-651, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37212707
ABSTRACT
We assess the longitudinal tumor growth inhibition (TGI) metrics and overall survival (OS) predictions applied to patients with advanced biliary tract cancer (BTC) enrolled in IMbrave151 a multicenter randomized phase II, double-blind, placebo-controlled trial evaluating the efficacy and safety of atezolizumab with or without bevacizumab in combination with cisplatin plus gemcitabine. Tumor growth rate (KG) was estimated for patients in IMbrave151. A pre-existing TGI-OS model for patients with hepatocellular carcinoma in IMbrave150 was modified to include available IMbrave151 study covariates and KG estimates and used to simulate IMbrave151 study outcomes. At the interim progression-free survival (PFS) analysis (98 patients, 27 weeks follow-up), clear separation in tumor dynamic profiles with a faster shrinkage rate and slower KG (0.0103 vs. 0.0117 week-1 ; tumor doubling time 67 vs. 59 weeks; KG geometric mean ratio of 0.84) favoring the bevacizumab containing arm was observed. At the first interim analysis for PFS, the simulated OS hazard ratio (HR) 95% prediction interval (PI) of 0.74 (95% PI 0.58-0.94) offered an early prediction of treatment benefit later confirmed at the final analysis, observed HR of 0.76 based on 159 treated patients and 34 weeks of follow-up. This is the first prospective application of a TGI-OS modeling framework supporting gating of a phase III trial. The findings demonstrate the utility for longitudinal TGI and KG geometric mean ratio as relevant end points in oncology studies to support go/no-go decision making and facilitate interpretation of the IMbrave151 results to support future development efforts for novel therapeutics for patients with advanced BTC.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias do Sistema Biliar
/
Neoplasias Hepáticas
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos