Abstract 3343: Durable response to osimertinib monotherapy as first line treatment in stage IVB lung adenocarcinoma with atypical EGFR L747P mutation
Authors: Choi Horyun , Lee Yeun Ho , Kim Jinah , Kim Leeseul , Kim Na Hyun , Chae Young Kwang 
Published: June 2022

Abstract
Background: Targeted therapy plays a critical role in NSCLC with a certain type of mutation. Osimertinib is a third generation EGFR tylosine kinase inhibitor (TKI) which is primarily indicated for NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. Although use of osimertinib is currently limited to patients with common EGFR mutations, it has been reported that patients with NSCLC harboring uncommon EGFR mutations demonstrated response to EGFR TKIs. Herein, we present a case of advanced adenocarcinoma of the lung with atypical EGFR L747P mutation that revealed a noteworthy durable response to osimertinib monotherapy as first line treatment. Case presentation: A 47-year-old woman with no smoking history presented with new-onset hemoptysis and cough. A chest CT scan showed a lobulated, spiculated 38 mm left upper lung mass with innumerable bilateral pulmonary nodules. CT-guided biopsy demonstrated adenocarcinoma of lung with PD-L1 1-2%. Subsequent PET-CT scan revealed hypermetabolic neoplasm in the left lower lobe with scattered area of abnormal focal FDG uptake within the liver. Brain MRI showed unremarkable findings. The patient was diagnosed with stage IVB adenocarcinoma of lung with multiple hepatic metastases. Circulating tumor DNA (ctDNA) NGS assay showed EGFR L747P [0.3% of variant allele frequency (VAF)] and tissue NGS assay revealed EGFR L747P missense variant c.2239_2240delinsCC (22.8% of VAF). The patient was started on osimertinib 80 mg daily. Follow up CT scan in six week demonstrated decrease in size of the left lower lobe lung mass to 32 mm. She has maintained durable SD for six months without any adverse effects. Most recent follow-up CT scan after eight months from the treatment demonstrated SD of the mass in the left lower lobe and less prominent numerous pulmonary nodules. Discussion: It has not been reported that osimertinib monotherapy is used as first line therapy in NSCLC with EGFR L747P mutation. We report the case of durable response to osimertinib in patients with advanced NSCLC with EGFR L747P mutation. Our case highlights the potential efficacy of osimertinib to NSCLC with atypical EGFR mutation. Although there was a clinical trial to explore clinical activity of osimertinib in patients with NSCLC harboring uncommon EGFR mutation, EGFR L747R mutation was not investigated at that time. To date, there are no ongoing clinical trials on the use of osimertinib in NSCLC with EGFR L747P mutation. Further investigations are warranted to confirm the efficacy of osimertinib in this type of mutation.
Citation Format: Horyun Choi, Yeun Ho Lee, Jinah Kim, Leeseul Kim, Na Hyun Kim, Young Kwang Chae. Durable response to osimertinib monotherapy as first line treatment in stage IVB lung adenocarcinoma with atypical EGFR L747P mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3343.