Outcomes and prognostic contributors in patients with mutated non-small cell pulmonary adenocarcinomas: a single institution experience.

Background: is the most frequently encountered driver mutation in advanced non-small cell lung cancer (NSCLC). With targeted therapy for the most common mutation p.G12C on the horizon, the aim of this study is to retrospectively report outcomes in patients with mutated NSCLC.

Methods: This was a retrospective chart review of 7 hospitals in Texas with reflex biomarker testing in all lung adenocarcinomas. Patients were included if they had pathologically diagnosed adenocarcinoma of any stage originating in the lung with molecularly confirmed driver mutation of any genotypic subtype. Twelve-month survival was assessed and compared between p.G12C and all other detected mutations. Other outcomes including impact of age, sex, smoking status, and pack years smoked were assessed to determine if they had prognostic significance on mortality in KRAS mutated patients.

Results: There were 58 patients diagnosed with mutated NSCLC, 63.8% were at an advanced stage at diagnosis, 55.8% of patients were female, and 82.8% were white. The median age was 72 [52-88] years, and 93.1% were either current or prior smokers. p.G12C was the most common mutation (44.8%). At diagnosis, patients with p.G12C had poorer performance statuses compared to other mutations. A total of 32 (55.2%) patients died, 26 with advanced disease. In this study, current smoking status (P=0.1652), pack years smoked (P=0.6597), age (P=0.5092), sex (P=0.4309), and underlying codon mutation controlling for stage (P=0.2287) did not impact survival. However, p.G12C had a numerically lower 12 months overall survival (OS) compared to all other mutations in both early stage (56.3% 90.9%) and advanced stage (25.0% 47.6%) disease. Of note, 16 (27.6%) patients had prior, concurrent, or second malignancies, but these did not significantly impact OS (P=0.7696).

Conclusions: This study did not find a prognostic difference with sex, smoking history, age, or p.G12C mutation. The patients in this cohort with p.G12C had a numerically lower 12-month overall survival in both early and advanced stage disease compared to other mutations, and over one-quarter had a notable history of previous and second primary malignancies.