Influence of Mutation on Survival in Patients With Advanced -Mutant Non-Small-Cell Lung Cancer.

Purpose: mutation (MT) in epidermal growth factor receptor () -MT non-small cell lung cancer (NSCLC) is associated with poor response to targeted therapy; however, its impact on survival is not clearly established.

Patients And Methods: We performed an analysis of patients with stage IV MT NSCLC with available gene sequencing data. Associations between baseline characteristics; molecular profile, including MT; and survival outcomes were assessed.

Results: We identified 131 consecutive patients with MT; 81 (62%) had a MT, and 55 (42%) had other coexisting oncogenic MTs. Emergent T790M MT was observed in 42 patients (32%). Overall survival (OS) was longer for younger patients ( = .003), never smokers ( = .002), those with Eastern Cooperative Oncology Group performance status 0 to 1 ( = .004), and emergent T790M MT ( = .018). MT ( = .021) and other coexisting oncogenic MTs ( = 0.011) were associated with inferior OS. In a multivariable regression analysis adjusted for age, smoking, Eastern Cooperative Oncology Group performance status, and the presence of MT ( = .063) and other coexisting MTs ( = .064) did not achieve statistical significance. Patients with T790M double MT had worse OS compared with patients with T790M MT alone (46.4 months 82.9 months). In our series, five patients transformed to small-cell lung cancer (5.6%). All had MT. In four patients, allelic fraction of MT increased at the time of transformation.

Conclusion: The presence of and other coexisting MTs in MT NSCLC were associated with inferior OS, including patients with emergent T790M MT. An increase in mutation allelic fraction may potentially be a useful clinical predictor of small-cell transformation.