Impact of and Co-Mutations on Outcomes After First-Line Systemic Therapy Among Patients With -Mutated Advanced Non-Small-Cell Lung Cancer.

Purpose: The gene encodes a serine/threonine protein kinase that regulates cell polarity and functions as a tumor suppressor. Patients with non-small-cell lung cancer (NSCLC) and mutations often have other co-mutations. We evaluated the impact of and co-mutations on outcomes after first-line systemic therapy for patients with metastatic or recurrent NSCLC that harbors mutations.

Methods: We conducted a retrospective review of patients with metastatic NSCLC and mutations treated at the University of Pennsylvania. mutations were identified through next-generation sequencing (NGS) in tissue or plasma. Cox proportional hazard models were used to determine the relationship between co-mutations and survival outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS).

Results: From February 2013 to December 2016, samples from 1,385 patients with NSCLC were analyzed by NGS; of these, 77 patients (6%) harbored an mutation (n = 56, tissue; n = 21, plasma). Of the 62 patients included, 18 had an mutation alone, 19 had 18 had and seven had Patients with co-mutations had a worse median PFS (2.4 months) compared with alone (5.1 months; log-rank = .048), (4.3 months; log-rank = .043), and (13 months; log-rank = .03). Patients with co-mutation experienced shorter median OS (7.1 months) compared with alone (16.1 months; log-rank .001), (28.3 months; log-rank < .001), and (22 months; log-rank = .025).

Conclusion: Among patients with advanced NSCLC and mutations treated with first-line systemic therapy, co-mutation with was associated with significantly worse PFS and OS. By contrast, co-mutation of with conferred a better prognosis.