BACKGROUND Lung cancer is the most common cancer worldwide in males & a good number of patients present with metastatic disease. Though EGFR mutated patients respond to EGFR TKIs, resistance develops ultimately. Overcoming 3rd generation EGFR TKI resistance is a big challenge. METHOD 20 patients of metastatic adenocarcinoma, confirmed with core biopsy & IHC (EGFR positive) were offered Erlotinib initially. Osimertinib was offered to those who developed EGFR TKI resistance due to T790M mutation (10 cases). All 10 patients eventually developed resistance to Osimertinib. All patients were given 3 months drug free holiday & then re-challenged with Erlotinib. RESULT 4 out of 10 (40%) patients responded to the therapy. 6 patients had progression & were managed by systemic chemotherapy & radiation. CONCLUSION Literature shows up to 50% metastatic adenocarcinoma, EGFR positive patients who had developed EGFR TKI resistance to 1st & 3rd generation TKIs, responds to re-challenge with first generation TKI after a drug free holiday. In this series 40% patients responded. This approach should be tried & non-responders can be offered systemic chemotherapy & radiation.

Citation Format: Suryakanta Acharya. Metastatic NSCLC -Re-challenging with first generation TKI after a drug free holiday after resistance to 3rd generation TKI [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P083.