Osimertinib and Abemaciclib in EGFR Mutant Non-Small Cell Lung Cancer After Osimertinib Resistance

Lung cancer is the leading cause of cancer deaths. Advances in the systemic treatment of non-small cell lung cancer (NSCLC) have increased survival in metastatic EGFR-mutated NSCLC. However resistance to therapy can develop. NSCLC tumors with EGFR-activating mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors with overall response rates approximating 80%. The third generation EGFR compound osimertinib is a standard first line option. Resistance to the third generation EGFR-TKI osimertinib can develop with a median PFS of 18.9 months. Current research examining acquired resistance to EGFR-TKIs has focused on overcoming these main mechanisms of EGFR-TKI resistance and understanding the impact of co-occurring alterations. Frequently altered pathways concomitantly affected with EGFR in lung cancer are cell cycle genes. This study will explore a strategy to inhibit EGFR and CDK4/6 in resistant EGFR mutated lung cancer patients post progression on osimertinib.