Determinants of Survival in Advanced Non-Small-Cell Lung Cancer in the Era of Targeted Therapies

Molecular profiling of non-small-cell lung cancer (NSCLC) samples is important for therapeutic decision-making, but its independent association with prognosis is unclear. We performed a retrospective chart review of patients with NSCLC undergoing EGFR and KRAS mutational testing at the Hospital of the University of Pennsylvania. A survival analysis revealed that neither EGFR nor KRAS held independent prognostic significance. This will help inform patient communication about prognosis. Background: Molecular profiling of non-small-cell lung cancer (NSCLC) samples has a profound impact on choice of therapy. However, it is less clear whether EGFR and KRAS mutations are prognostic outside of a trial-based treatment paradigm. Methods: We performed a retrospective chart review of 513 patients with NSCLC undergoing EGFR and KRAS mutational analysis at the Hospital of the University of Pennsylvania between May 2008 and November 2011. Survival analysis was based on the 376 patients who received systemic treatment, and their survival was determined from the date of initiation of systemic therapy. Results: The median overall survival (OS) was 30.8 months (95% confidence interval [CI], 24.7-36.9). Neither EGFR mutational status (P=.09) nor KRAS mutational status (0.69) was associated with OS. Female sex (P<.001), never smoker status (P=.01), better performance status (PS) (P<.001), lower Charlson Comorbidity Index (P<.001), and lower age-weighted index (P<.001) were associated with prolonged survival. The presence of bone metastases (P=.001) and liver metastases (P=.004) was also associated with a shortened survival. In a multivariable regression that adjusted for stage, we demonstrated that male gender (P=.002), worse Eastern Cooperative Oncology Group PS (P=.01), metastases to bone (P=.03), and higher age-weighted comorbidity index (P=.001) were independent prognostic factors for shorter survival. EGFR mutation status was not prognostic (P=.85). Conclusion: In our series, EGFR and KRAS do not function as prognostic determinants for NSCLC.