Correlation between nivolumab exposure and treatment outcomes in non–small-cell lung cancer. (March 2019)

• Record Type: Journal Article
• Authors: Basak, Edwin A.; Koolen, Stijn L.W.; Hurkmans, Daan P.; Schreurs, Marco W.J.; Bins, Sander; Oomen – de Hoop, Esther; Wijkhuijs, Annemarie J.M.; Besten, Ilse den; Sleijfer, Stefan; Debets, Reno; van der Veldt, Astrid A.M.; Aerts, Joachim G.J.V.; Mathijssen, Ron H.J.
• Is Part Of: European journal of cancer. Volume 109(2019)
• Page Start: 12
• Page End: 20
• Publication Date: 2019-03
• Subjects: Nivolumab -- NSCLC -- Drug exposure -- Pharmacokinetics; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.12.008
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Introduction: 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). 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 = 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). 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 exposure–response relationship. Further clinical research should focus on clarifying these exposure–response relationships. Highlights: 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.