Influence of germline variations in drug transporters ABCB1 and ABCG2 on intracerebral osimertinib efficacy in NSCLC patients

Central nervous system (CNS) metastases are present in approximately 40% of patients with metastatic non-small cell lung cancer with EGFR-mutations. The EGFR-TKI osimertinib is a substrate of transporters ABC1 and ABCG2. A multicenter retrospective trial in The Netherlands found that among patients with EGFRm+ NSCLC without baseline CNS-metastases at start of osimertinib, genotypes ABCG2 34GA/AA and/or ABCB1 3435CC, present in 35% of the patients, were associated with decreased CNS-DFS, probably because of diminished drug levels in the CNS. Pre-emptive genotyping for these SNPs could individualize osimertinib therapy.