%0 Journal Article
%T Mechanisms of resistance and correlation between pre-treatment co-alterations and p-prognosis to osimertinib in chemo-naïve advanced non-small cell lung cancer.
%A Tamiya A
%A Osuga M
%A Harada D
%A Isa SI
%A Taniguchi Y
%A Nakamura K
%A Mizumori Y
%A Shinohara T
%A Yanai H
%A Nakatomi K
%A Oki M
%A Mori M
%A Kuwako T
%A Yamazaki K
%A Tamura A
%A Ando M
%A Koh Y
%J Lung Cancer
%V 195
%N 0
%D 2024 Sep 3
%M 39116552
%F 6.081
%R 10.1016/j.lungcan.2024.107917
%X <B>BACKGROUND: </B>Several patients treated with osimertinib experience progressive disease. The aim was to clarify the mechanisms underlying resistance to osimertinib.<BR><B>METHODS: </B>ELUCIDATOR: A multi-centre, prospective, observational study involved chemotherapy-naive patients with advanced non-small cell lung cancer receiving osimertinib. Mutations in cancer-associated genes, detected via ultrasensitive next-generation sequencing of circulating tumour deoxyribonucleic acid samples, were collected at baseline and after progressive disease detection. These paired plasma samples were compared.<BR><B>RESULTS: </B>Of 188 patients enrolled (May 2019-January 2021), 178 (119 females [67 %]) median age 74 years, were included. Patients, n = 95 (53 %) had epidermal growth factor receptor exon 19 deletion mutations. Among 115 patients with progressive disease, circulating tumour deoxyribonucleic acid levels of 85 patients were analysed. MET amplification (n = 4), TP53 mutations (n = 4), PIK3CA mutations (n = 3), BRINP3 mutation (n = 2), BRAF mutation (n = 2), APC mutation (n = 1), RET mutation (n = 1) and epidermal growth factor receptor (EGFR) resistance mutation, and C797S (n = 1) were detected. Patients with baseline TP53 mutations, with MET or EGFR amplification had shorter progression-free (PFS) and overall survival. Patients with PIK3CA mutations tended to shorter PFS.<BR><B>CONCLUSIONS: </B>MET amplification and PIK3CA mutation mechanisms underly resistance to osimertinib in patients. Patients with coexisting mutations or amplifications at baseline had shorter PFS and overall survival.