Health-Related Quality of Life and Survival in Metastasized Non-Small Cell Lung Cancer Patients with and without a Targetable Driver Mutation

SIMPLE SUMMARY: NSCLC patients with a targetable driver mutation are entitled to receive targeted therapy. Targeted therapy is usually less toxic than chemotherapy and immunotherapy. However, low-grade side effects are common and often chronic, which could also negatively impact a patient’s health-related quality of life (HRQOL). HRQOL in NSCLC patients with and without a targetable driver mutation is thus likely to be different. To optimize clinical decision making for individualized treatment in patients with metastatic NSCLC, it is necessary to understand differences in HRQOL and survival outcomes between patients with and without a targetable driver mutation. In this study, we show that NSCLC patients with a targetable driver mutation have favorable HRQOL over time compared to patients without a targetable driver mutation. Furthermore, clinically relevant HRQOL declines over time were significantly associated with worse survival. HRQOL can therefore play an important role in shaping patients’ expectations of their prognosis. ABSTRACT: Background: The aim of this study is to compare long-term health-related quality of life (HRQOL) and survival in metastatic NSCLC patients with (M+) and without (M−) a targetable driver mutation. Methods: An observational study was performed within the prospective SYMPRO-lung study (NL7897). HRQOL questionnaires were completed at baseline, 15 weeks, and 6 months. Generalized estimating equations (GEE) were used to assess clinically significant declines in HRQOL (>10 points) over time. Kaplan–Meier survival curves were plotted for both progression-free survival (PFS) and overall survival (OS). Results: 81 metastatic NSCLC patients were included (M+ patients; 16 (20%)). M+ patients had a significantly better global HRQOL (mean difference 12.8, ES 0.61), physical functioning (mean difference 13.4, ES 0.63), and less appetite loss (mean difference 23.1, ES 0.73) at 15 weeks of follow-up compared to M− patients. Patients with a clinically relevant decline in HRQOL at 6 months of follow-up had a significantly shorter PFS (5 months vs. 12 months, p-value < 0.001) and OS (11 months vs. 16 months, p-value 0.002). Conclusions: M− NSCLC patients have less favorable HRQOL over time compared to M+ patients. Furthermore, clinically relevant HRQOL declines over time were significantly associated with worse survival. HRQOL can therefore play an important role in in shaping patients’ expectations of their prognosis.