Tumor Growth Inhibition-Overall Survival (TGI-OS) Model for Subgroup Analysis Based on Post-Randomization Factors: Application for Anti-drug Antibody (ADA) Subgroup Analysis of Atezolizumab in the IMpower150 Study.


Journal

The AAPS journal
ISSN: 1550-7416
Titre abrégé: AAPS J
Pays: United States
ID NLM: 101223209

Informations de publication

Date de publication:
28 04 2022
Historique:
received: 02 03 2022
accepted: 13 04 2022
entrez: 28 4 2022
pubmed: 29 4 2022
medline: 3 5 2022
Statut: epublish

Résumé

Longitudinal changes of tumor size or tumor-associated biomarkers have been receiving growing attention as early markers of treatment benefits. Tumor growth inhibition-overall survival (TGI-OS) models represent mathematical frameworks used to establish a link from tumor size trajectory to survival outcome with the aim of predicting survival benefit with tumor data from a small number of subjects with a short follow-up time. In the present study, we applied the TGI-OS model to assess treatment benefit in the IMpower150 study for patients who exhibited development of anti-drug antibodies (ADA). Direct comparison between subgroups of the active arm [ADA positive (ADA +) and negative (ADA -) groups] to the entire control group is not appropriate, due to potential imbalances of baseline prognostic factors between ADA + and ADA - patients. Thus, the TGI-OS modeling framework was employed to adjust for differences in prognostic factors between the ADA subgroups to more accurately estimate the treatment benefits. After adjustment, the TGI-OS model predicted comparable hazard ratios (HRs) of OS between ADA + and ADA - subgroups, suggesting that the development of ADA does not have a clinically significant impact on the treatment benefit of atezolizumab.

Identifiants

pubmed: 35484442
doi: 10.1208/s12248-022-00710-4
pii: 10.1208/s12248-022-00710-4
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
atezolizumab 52CMI0WC3Y

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

58

Informations de copyright

© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.

Références

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Auteurs

Kenta Yoshida (K)

Department of Clinical Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. yoshida.kenta@gene.com.

Phyllis Chan (P)

Department of Clinical Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.

Mathilde Marchand (M)

Certara Strategic Consulting, Certara, Paris, France.

Rong Zhang (R)

Department of Clinical Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.

Benjamin Wu (B)

Department of Clinical Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.

Marcus Ballinger (M)

Clinical Science, Genentech, Inc., South San Francisco, CA, USA.

Nitzan Sternheim (N)

Product Development, Genentech, Inc., South San Francisco, CA, USA.

Jin Y Jin (JY)

Department of Clinical Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.

René Bruno (R)

Clinical Pharmacology, Genentech-Roche, Marseille, France.

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