Early Decision Making in a Randomized Phase II Trial of Atezolizumab in Biliary Tract Cancer Using a Tumor Growth Inhibition-Survival Modeling Framework.
| Title: | Early Decision Making in a Randomized Phase II Trial of Atezolizumab in Biliary Tract Cancer Using a Tumor Growth Inhibition-Survival Modeling Framework. |
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| Authors: | Shemesh CS; Clinical Pharmacology, Genentech Inc., South San Francisco, California, USA.; Chan P; Clinical Pharmacology, Genentech Inc., South San Francisco, California, USA.; Marchand M; Certara Strategic Consulting, Paris, France.; Gonçalves A; Certara Strategic Consulting, Paris, France.; Vadhavkar S; Clinical Pharmacology, Genentech Inc., South San Francisco, California, USA.; Wu B; Clinical Pharmacology, Genentech Inc., South San Francisco, California, USA.; Li C; Clinical Pharmacology, Genentech Inc., South San Francisco, California, USA.; Jin JY; Clinical Pharmacology, Genentech Inc., South San Francisco, California, USA.; Hack SP; Product Development Oncology, Genentech Inc., South San Francisco, California, USA.; Bruno R; Clinical Pharmacology, Genentech-Roche, Marseille, France. |
| Source: | Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2023 Sep; Vol. 114 (3), pp. 644-651. Date of Electronic Publication: 2023 Jun 02. |
| Publication Type: | Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Wiley Country of Publication: United States NLM ID: 0372741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-6535 (Electronic) Linking ISSN: 00099236 NLM ISO Abbreviation: Clin Pharmacol Ther Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2015- : Hoboken, NJ : Wiley; Original Publication: St. Louis : C.V. Mosby |
| MeSH Terms: | Biliary Tract Neoplasms*/drug therapy ; Biliary Tract Neoplasms*/etiology ; Biliary Tract Neoplasms*/pathology ; Liver Neoplasms*; Bevacizumab/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/therapeutic use ; Humans ; Proportional Hazards Models ; Decision Making ; Antibodies, Monoclonal, Humanized |
| 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.; (© 2023 Genentech, Inc. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.) |
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| Substance Nomenclature: | 2S9ZZM9Q9V (Bevacizumab); Q20Q21Q62J (Cisplatin); 52CMI0WC3Y (atezolizumab); 0 (Antibodies, Monoclonal, Humanized) |
| Entry Date(s): | Date Created: 20230522 Date Completed: 20230821 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| DOI: | 10.1002/cpt.2953 |
| PMID: | 37212707 |
| Database: | MEDLINE |
Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't