Correlation between nivolumab exposure and treatment outcomes in non–small-cell lung cancer
| Autor: | Astrid A M van der Veldt, Esther Oomen-de Hoop, Stijn L.W. Koolen, Daan P. Hurkmans, Ilse den Besten, Edwin A. Basak, Marco W.J. Schreurs, Ron H.J. Mathijssen, Joachim G.J.V. Aerts, Annemarie J.M. Wijkhuijs, Reno Debets, Stefan Sleijfer, Sander Bins |
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| Přispěvatelé: | Medical Oncology, Pharmacy, Immunology, Pulmonary Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Adenocarcinoma of Lung 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Pharmacokinetics SDG 3 - Good Health and Well-being Carcinoma Non-Small-Cell Lung Internal medicine medicine Humans Trough Concentration Lung cancer Response Evaluation Criteria in Solid Tumors Aged business.industry Common Terminology Criteria for Adverse Events Middle Aged medicine.disease Survival Rate Nivolumab Treatment Outcome 030104 developmental biology Clinical research 030220 oncology & carcinogenesis Toxicity Carcinoma Squamous Cell Disease Progression Carcinoma Large Cell Female Analysis of variance business Follow-Up Studies |
| Zdroj: | European Journal of Cancer, 109, 12-20. Elsevier Ltd. |
| ISSN: | 1879-0852 0959-8049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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