This single-center phase II study aimed to examine the efficacy and feasibility of nivolumab for patients with advanced non-small cell lung cancer (NSCLC) who were unsuitable for single-agent chemotherapy or targeted agents because of their poor performance status (PS).
In this study, we enrolled previously treated patients with advanced NSCLC with poor PS of 2–4 without any indication of cytotoxic chemotherapy or targeted therapies. All enrolled patients received nivolumab (3 mg/kg, every 2 weeks) until progression or unacceptable toxicities. In addition, we prospectively obtained peripheral blood mononuclear cells (PBMC) and plasma from patients after obtaining their informed consent before treatment.
Between April 2016 and December 2017, we enrolled 33 patients with NSCLC and poor PS, including 23 patients with PS 3–4. In this study, the response rate was 29.0% (90% confidence interval (CI), 17.7%–43.7%), and the disease control rate was 41.9% in 31 evaluable patients. PS improvement rate was 29.0%. In addition, the median progression-free survival (mPFS), median overall survival (mOS), and 1-year survival rates were 1.5 (95% CI, 1.0–2.7) months, 3.8 (95% CI, 2.4–16.3) months, and 37.6%, respectively. Among patients harboring EGFR-mutations (mut), the mPFS was 2.6 and 1.1 months in EGFR-wild type (wt) and EGFR-mut (p = 0.015), respectively, and the mOS was 9.3 and 1.9 months in EGFR-wt and EGFR-mut (p = 0.029), respectively. During the study period, treatment-related deaths were observed in 2 patients (6.1%). We obtained blood samples from 75% of the enrolled patients (data will be updated in the meeting).
To the best of our knowledge, this is the first trial to investigate the efficacy of immune checkpoints in patients with advanced NSCLC with poor PS. Although the response rate was similar to those with good PS, shorter survival was observed. Excluding patients harboring driver mutations may enhance treatment efficacy to show a survival benefit even for poor PS patients. Nevertheless, the biomarker investigation warrants focus on the PBMC analysis.
Clinical trial identification
Clinical trial registration: UMIN000020855/UMIN000021734.
Legal entity responsible for the study
Tokyo Metropolitan Komagome Hospital.
Has not received any funding.
Y. Okuma: Research Funding: Chugai Pharma (Inst). Y. Hosomi: Honoraria: AstraZeneca; Boehringer Ingelheim Japan; Bristol-Myers Squibb Japan; Chugai Pharma; Eli Lilly Japan; Ono Pharmaceutical; Taiho Pharmaceutical; Research Funding: Chugai Pharma (Inst); Eli Lilly Japan (Inst); Ono Pharmaceutical. N. Yamamoto: Honoraria: AstraZeneca; Bristol-Myers Squibb Japan, Chugai Pharma, Eli Lilly Japan, Ono Pharmaceutical, Pfizer; Research Funding: Astellas Pharma (Inst), Bayer (Inst), Boehringer Ingelheim (Inst), Chugai Pharma (Inst), Daiichi Sankyo (Inst), Eisai (Inst), Kyowa Hakko Kirin (Inst), Eli Lilly Japan (Inst), Novartis (Inst), Pfizer (Inst), Quintiles (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst). All other authors have declared no conflicts of interest.