Representation of older patients in the safety analysis of protein kinase inhibitor registration studies

Introduction: Older patients (≥65 years old) make up the majority of the cancer population. Older patients seem to experience more adverse events (AEs) from protein kinase inhibitors (PKIs) in clinical practice. Yet they are underrepresented in clinical trials. We aimed to evaluate whether age-related safety differences were described at authorization of PKIs. Representation of older patients in registration studies was also evaluated.

Materials and methods: European Public Assessment Reports (EPARs) of PKIs authorized between 2010 and 2015 were evaluated for the description of age-related safety- and pharmacokinetic differences. The International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use (ICH) E7 guideline was applied to EPARs to assess the representation of older patients. Study results were presented descriptively.

Results: Eighteen PKIs with 19 EPARs were analyzed. Age-related safety differences were described in 14 out of 19 EPARs, and age-related pharmacokinetic differences in 1 out of 19 EPARs. More than 100 older patients were included in half of the studies. Older patients were not excluded solely by age, although other inclusion and exclusion criteria negatively influenced enrollment of older patients. None of the PKIs met all criteria from the ICH E7 guideline.

Discussion: Age-related safety differences are described for most PKIs. Older patients were underrepresented in PKI registration studies. Adequate representation of older patients in clinical trials for PKIs is vital, since they make up most of the cancer population.