Efficacy and safety of nivolumab in Japanese patients with advanced or recurrent squamous non‐small cell lung cancer

Abstract

Limited treatment options are available for stage IIIB/IV non‐small cell lung cancer (NSCLC). Nivolumab, a programmed cell death‐1 immune checkpoint inhibitor antibody, has been shown to be effective for the treatment of NSCLC. The present study investigated the effectiveness and safety of nivolumab in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum‐containing chemotherapy. In this multicenter phase II study, patients were treated with nivolumab (3 mg/kg, i.v.) every 2 weeks until progressive disease or unacceptable toxicity was seen. Primary endpoint was overall response rate (ORR) assessed by independent radiology review committee (IRC) and secondary endpoints included a study site‐assessed ORR, overall survival (OS), progression‐free survival (PFS), duration of response, time to response, best overall response (BOR), and safety. The study included 35 patients from 17 sites in Japan. Patients had IRC‐assessed ORR of 25.7% (95% CI 14.2, 42.1) and the study site‐assessed ORR was 20.0% (95% CI 10.0, 35.9). Median OS, median time to response and median PFS were 16.3 (95% CI 12.4–25.4), 2.7 (range 1.2–5.5) and 4.2 (95% CI 1.4–7.1) months, respectively. The IRC‐assessed BOR was partial response, stable disease, and progressive disease for 25.7%, 28.6%, and 45.7% of patients, respectively. Treatment‐related adverse events were reported in 24 patients (68.6%), most of which resolved with appropriate treatment including steroid therapy or ‎discontinuation of nivolumab. Nivolumab was effective and well tolerated in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum‐containing chemotherapy. Clinical trial registration number: JapicCTI‐132072

Three‐year follow‐up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non‐small cell lung cancer: Pooled analysis of ONO‐4538‐05 and ONO‐4538‐06 studies

“…Consequently, it was deemed important to assess the effects of nivolumab in the subset of patients expressing PD‐L1. The pooled results of efficacy by PD‐L1 expression in both SQ and non‐SQ NSCLC patients were consistent with those of the individual reports (ONO‐4538‐05, ONO‐4538‐06) . The 3‐year OS and PFS rates showed that, after 3 years of follow‐up, nivolumab continued to demonstrate long‐term efficacy in previously treated patients with SQ or non‐SQ NSCLC.…”

“…In this analysis of the ONO‐4538‐05 and ONO‐4538‐06 studies, the continued clinical efficacy of nivolumab in Japanese patients with either SQ or non‐SQ NSCLC noted in the primary phase II analysis of this study was reinforced. The safety profile was also found to be acceptable, consistent with that observed in the individual primary analyses …”

Effectiveness of Nivolumab versus Docetaxel as Second-Line Treatment in Non-Small Cell Lung Cancer Patients in Clinical Practice

“…The authors reported a PFS of 126 days (95% CI 42-213), which is higher than that obtained in our study. Even though Hida et al [15] included only squamous NSCLC patients, the confidence interval reported in their study overlapped the PFS value obtained in the present study.…”

Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab

“…Patients with advanced solid tumors who were treated with nivolumab from March 2009 through to March 2016 at the National Cancer Center Hospital (Tokyo, Japan) were eligible for this study. Subjects included patients who were treated in clinical practice as well as those who participated in sponsor‐initiated investigational trials (ONO‐4538‐01, ONO‐4538‐02, ONO‐4538‐04, ONO‐4538‐05, ONO‐4538‐06, and ONO‐4538‐08) . Patients were excluded from our study for the following reasons: previous treatment with any ICI, pre‐existing hypothyroidism such as thyroid‐stimulating hormone (TSH) >10 μIU/mL or concomitant treatment with levothyroxine replacement therapy before nivolumab, insufficient assessment for thyroid function and thyroid Abs, and a short follow‐up time of less than 90 days from the initial administration of nivolumab to exclude early progression and death.…”