Combination of the S49076 with gefitinib in NSCLC patients progressing on EGFR-TKI and harboring MET/AXL dysregulation

Abstract

Conclusions: Osimertinib has limited antitumor activity in patients with EGFR exon 20 mutated NSCLC, with an ORR of 6%. A subset of patients (35%) seems to derive benefit from osimertinib treatment with durable disease control for more than five months. Legal entity responsible for the study: J. de Langen. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. 1451P The characteristics and clinical outcome of metastatic NSCLC harboring uncommon EGFR mutation at Thailand's tertiary referral center Background: An uncommon EGFR-mutant NSCLC is a rare subset of NSCLC. Prevalence and clinical outcome of this entity remain unclear. Several studies have reported the benefit of EGFR-tyrosine kinase inhibitor in patients harboring complex or uncommon EGFR mutations but there are insufficient data to determine the advantage of EGFR-TKI over chemotherapy. This study aimed to review the prevalence and clinical outcome of treatment of uncommon EGFR-mutant patients in real-world practice. Methods: We retrospectively reviewed medical records of 681 patients tested for EGFR mutation NSCLC during 2014-2018 to collect the mutational status and to compare the survival outcomes between the patients treated with EGFR-TKI and chemotherapy. Results: At a median follow-up of 19.1 months, 317 (47%) patients were identified with EGFR-mutant NSCLC. Twenty-eight patients (8.8%) harbored uncommon EGFR mutations. Of those 28 patients, the most frequent single mutation was exon20 insertion (21%, n ¼ 6); 5 were L861Q and 4 were G719X. 13 (46%) patients had compound mutations: 4 were G719X plus S768I; 4 were de novo T790M plus either L858R or dele-tion(del)19; 2 were L858R plus del19; 1 was L858R plus Ex20Ins; 1 was del19 plus KRAS mutation, and 1 with G719X plus E709A was found in squamous cell carcinoma. History of tobacco use was found in 50% of patients. 100% of male patients with G719X mutation were smokers. 57% of the 28 patients were treated with EGFR-TKI, mostly 1 st generation, and 29% were treated with chemotherapy alone. The objective response rate was 56% in the TKI group. Median progression-free survival (PFS) in the TKI group was 10.2 months. 5-year overall survival (OS) rate was 34%. Patients treated with TKI had significantly better 5-year OS rate than those who had never received TKI (54% vs. 17%, 95%CI 1.23-14.66, p log-rank¼ 0.02). The longest OS was 73.6 months in a patient with del19 plus de novo T790M. Conclusions: T…