Inter-Ethnic Differences in the Efficacy and Safety of Tyrosine Kinase Inhibitors Used in Oncology: Insights From Phase 3 Clinical Trials

Differences in the efficacy and safety of tyrosine kinase inhibitors (TKIs) have been observed across ethnic/ancestry subpopulations (previously reviewed to 2017). With an expanding number of TKIs approved since that time, an updated review of TKI response across ethnic/ancestry subpopulations in Phase 3 TKI clinical trials was conducted. A total of 73 population subgroup analyses (defined by participant race, ethnicity, ancestry or geographic region) of progression-free survival (PFS) and/or overall survival (OS) were identified by a literature search. Twelve (16%) of the analyses investigating the efficacy of afatinib, brigatinib, dacomitinib, gilteritinib, lorlatinib, neratinib, osimertinib, or pazopanib were assessed to report population differences in PFS and/or OS. For 28 (38%) of the analyses that showed suggestions of a potential efficacy difference across subpopulations, limitations in the data available precluded further assessment. There were 17 (23%) analyses assessed to report comparable efficacy outcomes across diverse subpopulations. The majority of clinical trials noted no clinically remarkable differences in safety between subpopulations; however, for brigatinib, crizotinib, pazopanib, and sunitinib, distinct patterns of adverse events were reported in the Asian and non-Asian subgroups. The underrepresentation of specific subpopulations, the grouping together of results of diverse subpopulations, as well as inconsistencies in the definition and reporting of participant ethnicity/ancestry are barriers to the meaningful exploration of inter-ethnic differences in TKI response. Therefore, further insight into the associations between ethnicity/ancestry and TKI response will require an increase in the diversity of clinical trial participants and appropriate analysis and reporting of subpopulation results.