Safety and Cost Associated With Fixed-Dose Immunotherapy in Patients With Weight Extremes

Presenting Author: Christina Davis, PharmD, BCOP, University of Colorado Cancer Center, Aurora, CO

Co-Authors: Cali Lunowa, PharmD, University of Colorado Cancer Center, Aurora, CO; Moriah Cargile, University of Colorado Hospital, Aurora, CO

BACKGROUND: Nivolumab and pembrolizumab were initially approved with weight-based dosing of 3 mg/kg every 2 weeks and 2 mg/kg every 3 weeks, respectively. Later, the FDA approved fixed doses of 240 mg every 2 weeks or 480 mg every 4 weeks for nivolumab and 200 mg every 3 weeks or 400 mg every 6 weeks for pembrolizumab based on pharmacokinetic modeling showing similar areas under the curve compared with weight-based dosages.^1-3 However, patients of low and high weights represented a small percentage of the patients included in the simulations,^1,3 which led to questions regarding safety and cost implications in patients with weight extremes.³

OBJECTIVES: To compare the incidence of adverse events (AEs) in patients weighing ≤50 kg or ≥110 kg with the previously reported literature and to determine the cost implications of fixed dosing strategies.

METHODS: Retrospective review of adult patients receiving single-agent pembrolizumab or nivolumab for treatment of cutaneous malignancies within the UCHealth System between January 1, 2016, and May 30, 2024. Patients were included if they received ≥1 dose of nivolumab 240 mg or pembrolizumab 200 mg and weighed ≤50 kg or ≥110 kg. Data collection included baseline demographics, autoimmune disease, line of treatment, earlier treatments, immunotherapy received, dose administered, total number of doses administered per patient, and incidence of AEs. Treatment cost per patient was calculated using standard vial size and present-day vial cost provided from the internal purchasing department. Theoretical cost-savings using weight-based dosing instead of fixed-doses was calculated using the same vial sizes and cost.

RESULTS: A total of 95 patients were assessed, including 45 patients weighing ≤50 kg in the low-weight group (LWG) and 50 patients weighing ≥110 kg in the high-weight group (HWG). Nivolumab was administered to 67% in the LWG and 56% in the HWG. The mean number of fixed immunotherapy doses per patient was 10±12 for the LWG and 13±14 for the HWG. The observed incidence of AEs with immune checkpoint inhibitors was similar for each group when compared with the literature.^3-5 Fixed doses of nivolumab and pembrolizumab were associated with increased drug cost totaling $1.8 million when used for patients weighing ≤50 kg.

CONCLUSION: The implementation of weight-based nivolumab and pembrolizumab dosing for patients with low weight is a safe and efficient drug cost–saving strategy.

1. Freshwater T, Kondic A, Ahamadi M, et al. Evaluation of dosing strategy for pembrolizumab for oncology indications. J Immunother Cancer. 2017;5:43.
2. Zhao X, Suryawanshi S, Hruska M, et al. Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a 3-mg/kg dosing regimen in patients with advanced tumors. Ann Oncol. 2017;28:2002-2008.
3. Long GV, Tykodi SS, Schneider JG, et al. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018;29:2208-2213.
4. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320-330.
5. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521-2532.