- •Responders to nivolumab treatment had higher nivolumab exposure than progressors.
- •No difference in exposure was seen in patients with and without toxicity.
- •Factors influencing exposure should be clarified in future research.
Nivolumab treatment is subject to large interpatient variability in both efficacy and toxicity, which may partly be explained by differences in nivolumab exposure. Exposure–response relationships in regular healthcare have not been extensively investigated for nivolumab. Therefore, we aimed to identify possible exposure–response relationships in nivolumab-treated patients with non–small-cell lung cancer (NSCLC).
Patients with NSCLC who started second-line nivolumab therapy (3 mg/kg Q2W) between May 5th 2016 and August 1st 2017, and from whom serial blood samples, toxicity data and outcome data were prospectively collected, were included. Follow-up was carried out until November 1st 2017. Patients were classified according to the best overall response (BOR) based on the Response Evaluation Criteria in Solid Tumours, v1.1, and toxicities according to the Common Terminology Criteria for Adverse Events. Nivolumab trough concentrations were measured after 2, 4 and 10 weeks of treatment, excluding dose delays, and calculated geometric means were tested versus BOR or toxicity using analysis of variance and an independent samples t-test, respectively. Overall survival (OS) and progression-free survival were compared between high and low trough concentration groups.
Seventy-six patients were evaluable for analyses. Responders (n = 15) had higher mean trough concentrations than patients with progression (n = 33): 47% higher after 2 weeks (p = 0.001), 53% higher after 4 weeks (p = 0.008) and 73% higher after 10 weeks (p = 0.002). Higher trough concentrations were associated with longer OS (p = 0.001).
This study shows that patients with NSCLC with a response to nivolumab had a higher nivolumab exposure than patients with progression, indicating a potential exposure–response relationship. Further clinical research should focus on clarifying these exposure–response relationships.
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Published online: January 14, 2019
Accepted: December 5, 2018
Received in revised form: December 2, 2018
Received: October 4, 2018
© 2018 Elsevier Ltd. All rights reserved.
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- Letter to the Editor: Exposure–response or clearance–response relationship in immune checkpoint therapy?—A comment on ‘correlation between nivolumab exposure and treatment outcomes in non-small-cell lung cancer’ by Basak et alEuropean Journal of CancerVol. 114
- PreviewIn their manuscript, ‘Correlation between nivolumab exposure and treatment outcomes in non-small-cell lung cancer’, Basak et al  hypothesise that patients who were treated with nivolumab and exhibited stable disease and progressive disease would have benefited from an increased systemic exposure and propose that a higher dose of nivolumab should be considered for those patients. They arrive at this conclusion after evaluation of pharmacokinetic and outcome data in patients with non–small-cell lung cancer who all received a dose of 3 mg/kg, where some patients with higher trough concentrations experience a survival benefit.