2019
Correlation between nivolumab exposure and treatment outcomes in non-small-cell lung cancer
Publication
Publication
European Journal of Cancer , Volume 109 p. 12- 20
Introduction: Nivolumab treatment is subject to large interpatient variability in
both efficacy and toxicity, which may partly be explained by differences in nivolumab exposure. Exposureeresponse relationships in regular healthcare have not been extensively investigated for nivolumab. Therefore, we aimed to identify possible exposureeresponse
relationships in nivolumab-treated patients with nonesmall-cell lung cancer (NSCLC).
Methods: 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. Results: Seventy-six patients were evaluable for analyses. Responders (n Z 15) had higher
mean trough concentrations than patients with progression (n Z 33): 47% higher after 2 weeks
(p Z 0.001), 53% higher after 4 weeks (p Z 0.008) and 73% higher after 10 weeks (p Z 0.002).
Higher trough concentrations were associated with longer OS (p Z 0.001).
Conclusions: This study shows that patients with NSCLC with a response to nivolumab
had a higher nivolumab exposure than patients with progression, indicating a potential
exposureeresponse relationship. Further clinical research should focus on clarifying these
exposureeresponse relationships.
Additional Metadata | |
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doi.org/10.1016/j.ejca.2018.12.008, hdl.handle.net/1765/115367 | |
European Journal of Cancer | |
Organisation | Department of Medical Oncology |
Basak, E., Koolen, S., Hurkmans, D., Schreurs, M., Bins, S., Oomen - de Hoop, E., … Mathijssen, R. (2019). Correlation between nivolumab exposure and treatment outcomes in non-small-cell lung cancer. European Journal of Cancer, 109, 12–20. doi:10.1016/j.ejca.2018.12.008 |