Effect of polypharmacy on the outcomes of older patients with advanced non-small-cell lung cancer treated with PD-1/PD-L1 inhibitors: A retrospective cohort study

Introduction: The effect of polypharmacy on older patients with cancer is unclear. This study aimed to explore the effect of polypharmacy on the outcomes of treatment in older patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. Materials and Methods: We retrospectively reviewed the records of older patients (aged ≥65 years) with advanced NSCLC who received PD-1/PD-L1 inhibitors with or without platinum-based chemotherapy as first-line treatment from March 2016 to December 2020. Patients with driver oncogenes or Eastern Cooperative Oncology Group performance status (PS) ≥2 were excluded. Polypharmacy was defined as receiving five or more oral or inhaled medications at baseline. We compared the progression-free survival (PFS), overall survival (OS), and mean cumulative length of hospital stays between the polypharmacy and non-polypharmacy groups. Results: A total of 122 patients, with a median age of 72 years (range, 65–89 years), were included in the analysis. Of the patients, 34 (27.8%) had a PS of 0 and 68 (55.7%) had a PD-L1 tumor proportion score (TPS) of ≥50%. The median number of oral or inhaled medications was 4 (range, 0–12), and 60 (49.1%) patients were taking ≥5 medications (polypharmacy). Age and Charlson Comorbidity Index score were significantly higher in the polypharmacy group (P = 0.01 and P < 0.001, respectively). Compared with the non-polypharmacy group, the polypharmacy group had a similar median PFS (6.7 vs. 8.5 months, P = 0.94) and a shorter median OS (17.3 vs. 26.0 months, P = 0.04). In the polypharmacy group, the adjusted hazard ratio for OS (adjusted for age, PS, and PD-L1 TPS) was 1.65 (95% confidence interval, 1.04–2.86, P = 0.03). Patients in the polypharmacy group had longer hospital stays (46.3 ± 7.5 vs. 27.7 ± 4.1 days/person, P < 0.05) and more emergency hospitalizations (1.6 ± 0.3 vs. 0.8 ± 0.1 times/person, P < 0.05) during the first year. Discussion: Polypharmacy was associated with shorter survival time and longer hospitalization in older patients with advanced NSCLC receiving first-line immunotherapy with or without chemotherapy.