Prognostic impact of pretreatment T790M mutation on outcomes for patients with resected, EGFR-mutated, non-small cell lung cancer

Background Many previous studies have demonstrated that minor-frequency pretreatment T790M mutation (preT790M) could be detected by ultrasensitive methods in a considerable number of treatment-naive, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) cases. However, the impact of preT790M in resected cases on prognosis remains unclear. Methods We previously reported that preT790M could be detected in 298 (79.9%) of 373 surgically resected, EGFR-mutated NSCLC patients. Therefore, we investigated the impact of preT790M on recurrence-free survival (RFS) and overall survival (OS) in this cohort by multivariate analysis. All patients were enrolled from July 2012 to December 2013, with follow-up until November 30, 2017. Results The median follow-up time was 48.6 months. Using a cutoff value of the median preT790M allele frequency, the high-preT790M group (n = 151) had significantly shorter RFS (hazard ratio [HR] = 1.51, 95% confidence interval [CI]: 1.01-2.25, P = 0.045) and a tendency for a shorter OS (HR = 1.87, 95% CI: 0.99-3.55, P = 0.055) than the low-preT790M group (n = 222). On multivariate analysis, higher preT790M was independently associated with shorter RFS (high vs low, HR = 1.56, 95% CI: 1.03-2.36, P = 0.035), irrespective of advanced stage, older age, and male sex, and was also associated with shorter OS (high vs low, HR = 2.16, 95% CI: 1.11-4.20, P = 0.024) irrespective of advanced stage, older age, EGFR mutation subtype, and history of adjuvant chemotherapy. Conclusions Minor-frequency, especially high-abundance of, preT790M was an independent factor associated with a poor prognosis in patients with surgically resected, EGFR-mutated NSCLC.