Health-related quality of life in EGFR-mutant lung cancer survivors: SEER-MHOS analysis

Introduction: The proportion of lung cancer among never-smokers is rising, with EGFR mutations observed in approximately 40-60% of these cases. Given that EGFR-mutated (EGFRmt) lung cancer is more prevalent in non-smokers, females, and individuals of Asian ancestry, their survivorship needs likely differ from the typical lung cancer cohort, which primarily consists of older males with a history of heavy smoking. This study examined the mental and physical health outcomes, including perceived changes in health status, among three distinct groups: EGFRmt lung cancer patients, non-EGFRmt lung cancer patients and non-cancer controls. Methods: We utilized linked data from SEER registries, the Medicare Health Outcomes Survey (MHOS), and Medicare Part D prescription records to identify adults aged ≥65 years with lung cancer and receipt of EGFR tyrosine kinase inhibitors (TKIs) between 2007 and 2020. We identified non-EGFRmt lung cancer patients matched to EGFRmt cases by diagnosis year and cancer stage. Non-cancer controls were selected by matching to all lung cancer patients on survey age and survey year. Primary outcomes included (1) mental and physical health, assessed using the Veterans RAND instrument, and (2) perceived changes in mental and physical health compared with the previous year. Primary outcome information was derived from the MHOS survey nearest to the initial lung cancer diagnosis. Multinomial logistic regression models were applied to identify survivorship needs among EGFRmt and other lung cancer patients relative to non-cancer controls, adjusting for sex, race, and smoking status. Results: A total of 130 EGFRmt lung cancer patients, 520 non-EGFRmt patients, and 650 non-cancer controls were identified. EGFRmt patients were more frequently female (65% vs. 49% of non-EGFRmt patients and 62% of non-cancer controls), of Asian ancestry (18% vs. 4.8% and 4.5%), and less likely to be active smokers (13% vs. 25% and 7.4%). In adjusted multinomial logistic models, EGFRmt patients had a 1.20-fold higher likelihood of poor mental health (odds ratio [OR] = 1.20, 95% CI 1.02-1.39), while non-EGFRmt patients had a 1.14-fold higher likelihood (OR = 1.14, 95% CI 1.04-1.26), relative to non-cancer controls. Similarly, EGFRmt patients were most likely to report worsened mental health compared with non-cancer controls (OR = 2.81, 95% CI 1.66-4.76), whereas non-EGFRmt patients also demonstrated an elevated risk, though to a lesser degree (OR = 1.86, 95% CI 1.30-2.67). Across all lung cancer patients, poor outcomes in social and physical functioning, vitality, bodily pain, and general health were more prevalent than among non-cancer controls. Conclusion: Patients with EGFRmt lung cancer experience more deterioration of mental health than other lung cancer patients and non-cancer individuals. Targeted mental health interventions may improve long-term survivorship outcomes in this growing patient population.