Biomarker analysis of a phase II trial of cabozantinib and erlotinib in patients (pts) with EGFR-mutant NSCLC with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance: A California Cancer Consortium Phase II Trial (NCI 9303).

Abstract

8087 Background: Modulation of the MET and VEGFR signaling pathways are associated with resistance to EGFR TKI therapy in addition to acquired T790M mutation (mt). Cabozantinib is a TKI that targets MET and VEGFR2, and RET, AXL, IT and TIE-2. Third generation EGFR inhibitors are effective in T790M mt-pos tumors, although treatment of T790M-neg disease remains an area of unmet need. Cabozantinib and erlotinib in EGFRmt-positive NSCLC following PD on EGFR TKI showed benefit, and we evaluated potential mechanisms of resistance to therapy. Methods: Pts with EGFR mt and PD on an EGFR TKI immediately prior to enrollment were eligible. Erlotinib 150 mg daily + cabozantinib 40 mg daily were given on a 28 day cycle and ORR was the primary objective. Pts were required to have archival tissue available, and a subset had biopsy samples post-progression on EGFR TKI. MET amplification was determined by FISH and EGFRmt, including T790M, was analyzed by next-generation sequencing. Results: 37 pts were enrolled and baseli...