P3.16-03 Uncommon EGFR Mutations as a Worse Prognostic Factor for Surgically Resected Lung Adenocarcinoma

Abstract

The characteristics and prognosis of patients with lung adenocarcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations have not been clarified. Here, we examined whether the presence of uncommon EGFR mutations is a prognostic factor for patients treated surgically. In this multi-institutional retrospective cohort study, clinicopathological data were collected from 1,463 patients who underwent complete surgical resection for lung adenocarcinoma between 2005 and 2012 at five institutions and were examined for EGFR mutation status. Differences in postoperative overall survival (OS) and recurrence-free survival (RFS) according to EGFR mutation status were evaluated. Of 1,031 eligible patients, 500 (48.5%), 497 (48.2%), and 34 (3.3%) had wild-type EGFR (WT), common EGFR mutations (CMs), and uncommon EGFR mutations (UCMs), respectively. In the UCM group, 19 patients had a single mutation, including exon 18 G719X (n = 7), exon 20 T790M (n = 6), or exon 21 L861Q (n = 5), and 15 patients had compound mutations. The clinicopathological characteristics were not significantly different between the CM and UCM groups. The 5-year OS rates in the WT, CM, and UCM groups were 76.3%, 88.6%, and 68.4%, respectively. OS was significantly shorter in the UCM than CM group (p = 0.011), although no significant difference was observed between the UCM and WT groups (p = 0.83). The 5-year RFS rates in the WT, CM, and UCM groups were 63.7%, 75.4%, and 58.1%, respectively. RFS was significantly shorter in the UCM than CM group (p = 0.006), although no significant difference was observed between the UCM and WT groups (p = 0.41). The use of EGFR–tyrosine kinase inhibitors after recurrence did not affect the prognosis with respect to EGFR mutation type. Among those with single mutations in the UCM group, patients harboring T790M were younger, more likely to be males and smokers, and more likely to have a larger tumor size, lymph node metastasis, pleural invasion, and lymphovascular invasion, compared with those harboring G719X or L861Q. T790M was also associated with shorter OS and RFS; the 3-year OS rates were 50.0%, 83.3%, and 100% and the 3-year RFS rates were 16.7%, 71.4%, and 80.0% for patients harboring T790M, G719X, and L861Q, respectively. Among patients with surgically resected lung adenocarcinoma, OS and RFS were significantly shorter in those with UCMs compared with CMs, implying that UCMs may be a worse prognostic factor.