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Therapeutic drug monitoring of nivolumab in clinical practice: Preliminary experience.

e14089 Background: Fixed dose schemes, regardless of body weight, have been accepted by the regulatory agencies for the PD-1 targeting antibodies. Zaho X. and Ratain M. have elucidated that the mean steady state concentrations of nivolumab (N) at flat-doses of 240 mg Q2W or 480 mg Q4W were 57 µg/mL and 47 µg/mL, respectively. These levels are very similar to those observed at the dosage of 3 mg/kg Q2W. Considering the long half-life of N, its mechanism of action and the absence of correlation between exposure and response or toxicity at clinically tested doses, other schemes can be explored. Moreover, therapeutic drug monitoring (TDM) can contribute to individualize and optimize dosage. We determined serum N levels in patients with solid tumors. Methods: The PK profile of N was analyzed in 15 patients with solid tumors who received 3 mg/kg Q2W from May 2017 through January 2019. Eligible patients had non-small-cell lung cancer (n = 7), urothelial cancer (n = 1), gastric cancer (n = 1), breast cancer (n = 1), renal cell cancer (n = 1), colorectal cancer (n = 1), prostate cancer (n = 1), melanoma (n = 1) and sarcoma (n = 1). Free N serum concentrations were determined with a quantitative ELISA capable of detecting ≥ 0.3 µg/mL (Shikari Q-Nivo, Matriks Biotek, Ankara, Turkey). A total of 28 TDM were done after steady state (6th and 26th cycle). Results: For different reasons, 9 patients received N at 3, 4, 5, 6 or 7 week intervals once the steady state was reached. In these patients, a median reduction of 20.8% (6.7% - 43.0%) of the received doses was observed. Mean plasma concentrations of N observed after administration every 2 weeks was 73.5±32.5 µg/mL (n = 9). Once the steady state was reached, mean plasma concentrations at 3, 4, 5, 6 or 7 weeks, were 54.0±1.3 µg/mL (n = 2), 45.1±25.3 µg/mL (n = 7), 42.9±29.5 µg/mL (n = 5) and 24.4±11.7 µg/mL (n = 5), respectively. No statistically significant differences were observed in the serum levels of N between the dosing intervals of 3, 4 and 5 weeks and the standard regimen (Q2W) (p > 0.05). These data are similar to those described by Long G.V. et al. that compared N pharmacokinetic exposure for the 480 mg Q4W schedule simulated in 3817 patients across multiple tumor types with those for the 3 mg/kg Q2W and 240 mg Q2W schedules. Conclusions: The incorporation of the TDM of N in routine clinical practice could help to maintain a therapeutic drug plasma concentration with lower or less frequent doses, adding a financial benefit, without decreasing clinical efficacy. Further randomized trials to explore alternative dosing schemes of N, including personalization through TDM, are warranted