Targeting G1 S phase cell cycle alterations with CDK4/6 inhibitor based genomically matched personalized therapy approach.

3623Background: Although CDK4/6 inhibitors are established as a standard treatment option for hormone receptor-positive, HER2-negative metastatic breast cancer patients, its benefit in other solid tumors is unclear. Moreover, no clear biomarker exists that predicts the response to CDK4/6 inhibitors. Herein, we investigated the factors associated with clinical outcomes from CDK4/6 inhibitor-based therapy, used alone or in combination with other therapies targeting genomic co-alterations, among diverse cancer patients with potentially sensitizing alterations in G1-S phase cell-cycle alterations (defined as CDK4/6 amplifications, CCND1/2/3 amplifications or CDKN2A/B alterations). Methods: We interrogated molecular profiles of 2,457 patients with diverse solid tumors for G1-S phase cell-cycle alterations and co-altered genes using clinical-grade next generation sequencing (182-465 genes). Results: G1-S phase …