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.
Keywords: anti-drug antibody; atezolizumab; nonlinear mixed effect modeling; tumor growth inhibition.
© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.