1531P - Evaluation of the interindividual variability in plasma nivolumab level in non-small-lung cancer outpatients: preliminary results

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Alicja Puszkiel
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors A. Puszkiel1, G. Noé2, P. Boudou-Rouquette3, C. Le Cossec4, J. Arrondeau3, J.S. Giraud1, J. Alexandre3, M. Vidal5, F. Goldwasser3, B. Blanchet1
  • 1Functional Unit Of Pharmacokinetics And Pharmacochemistry, Hôpital Cochin, 75014 - Paris/FR
  • 2Umr 8638 Cnrs, Paris Descartes University, 75006 - Paris/FR
  • 3Department Of Medical Oncology, Cochin Hospital, Paris Descartes University, Ap­hp, Carpem, Certim, Hôpital Cochin, 75014 - Paris/FR
  • 4Domu, Assistance Publique - Hopitaux De Paris, Paris/FR
  • 5Functional Unit Of Pharmacokinetics And Pharmacochemistry, Paris Descartes University, Umr 8638 Cnrs, Hôpital Cochin, 75014 - Paris/FR

Abstract

Background

Nivolumab, an anti PD-1 inhibitor, has been approved for the treatment of previously treated advanced or metastatic non-small-cell-lung cancer (NSCLC). The response rate is about 20% with nivolumab. The inter-patient variability in clinical outcomes to nivolumab is large and could be influenced by its pharmacokinetics. However, no data is currently available about the inter-patient variability in plasma exposure to nivolumab in NSCLC outpatients. The aim was to investigate the inter-patient variability in plasma level of nivolumab from 27 NSCLC outpatients.

Methods

NSCLC patients were treated with nivolumab (3 mg/kg) every two weeks. Blood samples were collected just before the infusion on days 0 (baseline), 14, 28 and 42 after treatment start. Plasma trough levels (Cmin) of nivolumab were assayed with home-made ELISA. Univariate linear regression models were performed in order to explain the inter-patient variability in nivolumab Cmin on day 42. Multivariate model included all variables which were significant at the 10% level in the univariate analyses.

Results

The calibration for nivolumab assay was linear in the range 5-100 µg/mL. Intra- and interday imprecision for three internal quality controls (5, 20 and 75 µg/mL) were less than 9 and 12%, respectively. The median age of the cohort was 68 years (range 41-84) and the sex ratio (female/male) 1.27. The median dose of nivolumab was 207 mg (range 147-288). No nivolumab was detected in baseline samples. The mean nivolumab Cmin was 17.3 ± 4.8 µg/mL (CV = 27.8%), 25.0 ± 9.7 µg/mL (CV = 38.8%) and 33.0 ± 12.9 µg/mL (CV = 39.1%) on days 14, 28 and 42, respectively. A significant variation in nivolumab Cmin was observed over the time (one-way Anova test, p 

Conclusions

These preliminary results highlight a large inter-patient variability in nivolumab Cmin in NSCLC outpatients. Further PK/PD investigations are warranted to identify the influence of this pharmacokinetic variability on clinical outcomes.

Clinical trial identification

Not applicable

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.