The Predictive Values Of Mutation Patterns, Concurrent Mutations And Efficacy Of Different Generations Of Egfr-Tkis In Advanced Non-Small Cell Lung Cancer Harboring Non-Resistant Uncommon Egfr Mutations.

e21612 Background: The efficacy of EGFR-TKIs in patients with non-resistant uncommon EGFR mutations is controversial. The predictive values of mutation patterns, the presence of concurrent mutations and the choice of different generations of EGFR-TKI have not been well elucidated. Methods: We retrospectively enrolled 190 NSCLC patients with non-resistant uncommon EGFR mutations, defined as mutations other than single L858R, 19del, T790M or 20ins. Among them, 72 were advanced/recurrent patients who received 1st (N = 55) or 2nd generation (N = 17) EGFR-TKIs as first-line therapy and with retrievable PFS data; therefore, were enrolled for subsequent survival analyses. Results: Patients were categorized according mutation patterns: group1 patients harboring EGFR uncommon mutation in combination with EGFR 19 del/L858R; group 2 patients harboring single or complex EGFR uncommon mutations. Our analyses revealed that the median PFS (mPFS) of group 1 was significantly longer than those in groups 2 (14.65months vs 8.05 months; P = 0.004). Next, we investigated whether the presence of concurrent mutations in tumor suppressor genes or oncogenes would affect PFS. The mPFS of patients with no concurrent mutation, patients with concurrent tumor-suppressor genes mutations and patients with concurrent oncogenic driver mutations were 13.57m, 8.05m and 16.92m, respectively (p = 0.04). Patients with no concurrent mutation had a significantly longer mPFS than patients with concurrent tumor-suppressor genes mutations (p = 0.013). Collectively, multivariate analysis revealed that patients receiving 2nd generation TKI (p = 0.006, HR:0.277,95%CI:0.112-0.688) and coexist with 19del/L858R (p < 0.001, HR: 0.148,95% CI:0.065-0.333) were independently associated with favorable PFS; while concurrent TP53 mutation was independently associated with worse PFS (p = 0.008, HR: 2.530,95% CI:1.270-5.042). Conclusions: Our study revealed NSCLC patients harboring non-resistant uncommon EGFR mutations in combination with 19del/L858R were associated with favorable PFS. The presence of concurrent tumor-suppressor genes mutations especially TP53 is associated with worse prognosis. Patients treated with 2nd generation EGFR-TKI showed a longer PFS than those treated with 1st generation TKI.