Tumor Growth Inhibition-Overall Survival Subgroup Analysis of Atezolizumab in the IMpower150 Study

• Published in: The AAPS journal Vol. 24; no. 3
• Main Authors: Yoshida, Kenta, Chan, Phyllis, Marchand, Mathilde, Zhang, Rong, Wu, Benjamin, Ballinger, Marcus, Sternheim, Nitzan
• Format: Journal Article
• Language: English
• Published: Springer 01.05.2022
• Subjects: Biopharmaceutics; Drug therapy; Medical research; Medicine, Experimental; Operating systems; Patient outcomes; Prognosis; Tumors
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-022-00710-4

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. Graphical abstract