Associations of frailty with survival, hospitalization, functional decline, and toxicity among older adults with advanced non-small cell lung cancer.

Introduction: Among older adults with cancer receiving chemotherapy, frailty indices predict OS and toxicity. Given the increased use of immunotherapy and targeted therapy for advanced non-small cell lung cancer (aNSCLC), we evaluated frailty and Karnofsky Performance Status (KPS) among older adults with aNSCLC receiving chemotherapy, immunotherapy, and/or targeted therapy.

Methods: Patients aged ≥ 65 with aNSCLC starting systemic therapy with non-curative intent underwent geriatric assessments over 6 months. We developed a deficit-accumulation frailty index to categorize patients as robust, pre-frail, or frail. To evaluate associations between frailty and KPS with OS, we used Cox proportional hazards models adjusted for race, insurance, and treatment. We used logistic regression to evaluate hospitalizations, functional decline, and severe toxicity.

Results: Among 155 patients (median age 73), 45.8% were robust, 36.1% pre-frail, and 18.2% frail; 34.8% had a KPS ≥ 90, 32.9% had a KPS of 80, and 32.3% had a KPS ≤ 70. The median OS was 17.9 months. Pre-frail/frail patients had worse OS compared to robust patients (adjusted hazard ratio [HR] 2.09, 95% CI, 1.31-3.34) and were more likely to be hospitalized (adjusted odds ratio [OR] 2.21, 95% CI, 1.09-4.48), functionally decline (adjusted OR 2.29, 95% CI, 1.09-4.78), and experience grade ≥ 3 hematologic toxicity (adjusted OR 5.18, 95% CI, 1.02-26.03). KPS was only associated with OS.

Conclusions: Our frailty index was associated with OS, hospitalization, functional decline, and hematologic AEs among older adults with aNSCLC receiving systemic therapies, while KPS was only associated with OS. Pretreatment frailty assessment may help identify older adults at risk for poor outcomes to optimize decision-making and supportive care.