Multicenter Pharmacokinetic and Pharmacodynamic Study of Pembrolizumab for Non‐small‐Cell Lung Cancer in Patients Aged 75 Years and Older

Abstract

Pembrolizumab is a major treatment for recurrent or advanced non‐small‐cell lung cancer (NSCLC). However, data on its use and pharmacokinetics (PK) in older patients are limited. This open‐label, multicenter, observational study evaluated real‐world data on the safety, efficacy, and PK of pembrolizumab in older patients with NSCLC. In 99 patients aged ≥75 years, PK was determined by liquid chromatography–mass spectrometry on pretreatment samples. Performance status (PS), geriatric assessment (GA), overall response rate (ORR), progression‐free survival (PFS), and overall survival (OS) were evaluated. The median age was 78 (75–87) years. PS was 2–3 in 14 patients. The median ORR, PFS, and OS were 47.5%, 8.0, and 20.5 months, respectively. Although PK and ORR were not significantly associated, patients with the lowest Cycle 1‐trough quartile (Q1) experienced poorer PFS (Q1 vs. Q2–4; 3.4 vs. 11.8 months, P = 0.006) and OS (Q1 vs. Q2–4; 9.9 vs. 21.7 months, P = 0.005) than in other quartiles overall, and even in the PD‐L1 ≥50% subset (PFS, Q1 vs. Q2–4; 4.1 vs. 14.7 months, P = 0.005; OS, Q1 vs. Q2–4; 9.4 vs. 22.1 months, P = 0.010). The Q1 subgroup was characterized by poor PS and lower albumin, and more frequent “weight loss ≥ 10%” on the GA. Pembrolizumab therapy had similar PK and efficaciousness in older as well as younger patients. In patients with PS ≥2, low albumin, and vulnerable GA, early increases in PK levels are less likely, potentially diminishing efficacy even when PD‐L1 ≥50%.