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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. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors have emerged as a standard of care treatment for non-small cell lung cancer (NSCLC). To get insight into variations in tumour growth kinetics and their potential predictive values for outcome, we evaluated tumour growth rate (TGR) in patients receiving programmed cell death 1 (PD-1) checkpoint inhibitors., Patients and Methods: Differences in TGR before and after the start of treatment were calculated by entering the sum of the longest diameters from computer tomography scans before and after the initiation of therapy into a formula that assumes volumetric exponential tumour growth. TGR variations, possible predictors for TGR changes and its relationship to overall survival (OS) were studied. For comparison, tumour response was assessed using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1., Results: Among the 58 evaluable patients, 37 patients (64%) showed deceleration of TGR and 16 patients (27%) showed an acceleration of TGR after initiation of therapy, with a significant difference in median OS of 18.0 months versus 6.0 months (hazard ratio 0.35, 95% CI 0.18-0.71) between these groups. Four patients (7%) were defined as having hyperprogressive disease. In five patients (9%), tumour growth remained stable. These TGR categories were not significantly different according to age, sex, histology, smoking or previous radiotherapy. Of the patients defined as having progressive disease by RECIST version 1.1 at first follow-up, 40% showed response to checkpoint inhibitors by a decrease in TGR., Conclusion: Tumour growth kinetics can be used as a clinically relevant predictor for OS in anti-PD-1-treated patients with NSCLC, and may provide additional information to RECIST measurements., Competing Interests: Conflict of interest: D.M.H.J. ten Berge has nothing to disclose. Conflict of interest: D.P. Hurkmans has nothing to disclose. Conflict of interest: I. den Besten has nothing to disclose. Conflict of interest: J.S. Kloover has nothing to disclose. Conflict of interest: R.H.J. Mathijssen has nothing to disclose. Conflict of interest: R.J.E.M.A. Debets has nothing to disclose. Conflict of interest: E.F. Smit has nothing to disclose. Conflict of interest: J.G.J.V. Aerts has nothing to disclose., (Copyright ©ERS 2019.)