Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients with Unresectable Advanced or Recurrent Non-Small Cell Lung Cancer: An Exploratory Study of J-TAIL

Introduction This study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg Q3W regimen. Methods A subgroup of 262/1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August, 2018 to October, 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles (Q) 1-4; and their association with effectiveness; and the association between atezolizumab maximum plasma concentrations (Cmax) calculated using the existing PopPK model and AEs of special interest (AESIs). Results Overall, 175/262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (ECOG-PS ≥2, 12.0%; age ≥75 years, 28.9%; atezolizumab as ≥third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival (OS) was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 vs Q2-Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated Cmax at Cycle 1 increased. Conclusions In real-world Japanese patients with unresectable advanced/recurrent NSCLC, pharmacokinetics were similar to previous reports. Certain patient populations had shorter OS, and atezolizumab plasma concentrations in Cycle 3 were lower in this population. Elevated Cmax at Cycle 1 may be associated with an increased frequency of AESIs.