Local therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors

Abstract

7527 Background: The utility of EGFR directed therapy for the treatment of EGFR mutant lung cancer is limited by the development of acquired resistance (AR) to EGFR tyrosine kinase inhibitor (TKI) therapy, which occurs after a median of 16 months (mos). There are no approved targeted therapies after disease progression on EGFR TKI therapy. Local therapy for oligometastatic disease is used with regularity in other solid tumors, and can lead to long term survival in selected individuals. EGFR mutant lung cancers with AR to TKI therapy can follow an indolent course that is amenable to local therapy to treat progression of disease when used in conjunction with continued EGFR inhibition. Outcomes following local therapy in this setting have not been assessed. Methods: Patients (pts) with AR to EGFR TKI’s who received local therapy excluding treatment of CNS metastases or local therapy prior to AR were identified in an IRB-approved prospective registry of 184 pts with AR enrolled from August 2004- November 2011. We collected treatments as well as progression free survival (PFS) and overall survival (OS) after local therapy. Results: 18 pts received local therapy. Treatments included surgical resection and radiation to lung, lymph nodes, adrenal gland or bone. Median age was 57, 56% were women, and 61% were never smokers. 14 had EGFR Exon 19 deletions, and 4 L858R. The median time to development of AR on TKI was 19 mo (range 5-33). Known mechanisms of AR included T790M (11 pts), MET amplification (1 pt) and small cell transformation (1 pt). The median PFS after local therapy was 10 mo (95% CI: 4-NA), median time from local therapy until change in systemic therapy was 22 mo (95%CI: 6 - 30), and median OS from local therapy was 41 mo (95% CI: 26-NA). Local therapy was tolerated well, with 85% of pts restarting TKI therapy within one month of completing local therapy. Conclusions: Local therapy is well tolerated and in combination with continued EGFR TKI therapy prolongs time until change in systemic therapy is required and may lead to outcomes that are superior to currently available treatment options in selected individuals.