The population pharmacokinetics of atezolizumab demonstrate that the trough concentrations are well above the putative target of 6 µg/ml. Thus, alternative dosing schedules are indeed of interest, focusing on reducing the frequency to allow greater patient convenience and reduced costs.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Similar content being viewed by others
Morrissey KM, Marchand M, Patel H, Zhang R, Wu B, Chan HP, Mecke A, Girish S, Jin JY, Winter HR, Bruno R (2019) Alternative dosing regimens for atezolizumab: an example of model-informed drug development in the postmarketing setting. Cancer Chemother Pharmacol. https://doi.org/10.1007/s00280-019-03954-8
Ratain MJ, Goldstein DA, Lichter AS (2019) Interventional pharmacoeconomics: a new discipline for a cost-constrained environment. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2019.1341
Ratain MJ, Goldstein DA (2018) Time is money: optimizing the scheduling of nivolumab. J Clin Oncol. https://doi.org/10.1200/JCO.18.00045:JCO1800045
Deng R, Bumbaca D, Pastuskovas CV, Boswell CA, West D, Cowan KJ, Chiu H, McBride J, Johnson C, Xin Y, Koeppen H, Leabman M, Iyer S (2016) Preclinical pharmacokinetics, pharmacodynamics, tissue distribution, and tumor penetration of anti-PD-L1 monoclonal antibody, an immune checkpoint inhibitor. MAbs 8(3):593–603. https://doi.org/10.1080/19420862.2015.1136043
Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515(7528):558–562. https://doi.org/10.1038/nature13904
Spigel DR, Gettinger SN, Horn L, Herbst RS, Gandhi L, Gordon MS, Cruz C, Conkling P, Cassier PA, Antonia SJ, Burris HA, Fine GD, Mokatrin A, Kowanetz M, Shen X, Chen DS, Soria J-C (2013) Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). J Clin Oncol 31(15):8008. https://doi.org/10.1200/jco.2013.31.15_suppl.8008
Li H, Yu J, Liu C, Liu J, Subramaniam S, Zhao H, Blumenthal GM, Turner DC, Li C, Ahamadi M, de Greef R, Chatterjee M, Kondic AG, Stone JA, Booth BP, Keegan P, Rahman A, Wang Y (2017) Time dependent pharmacokinetics of pembrolizumab in patients with solid tumor and its correlation with best overall response. J Pharmacokinet Pharmacodyn 44(5):403–414. https://doi.org/10.1007/s10928-017-9528-y
Liu C, Yu J, Li H, Liu J, Xu Y, Song P, Liu Q, Zhao H, Xu J, Maher VE, Booth BP, Kim G, Rahman A, Wang Y (2017) Association of time-varying clearance of nivolumab with disease dynamics and its implications on exposure response analysis. Clin Pharmacol Ther 101(5):657–666. https://doi.org/10.1002/cpt.656
Ogasawara K, Newhall K, Maxwell SE, Dell’Aringa J, Komashko V, Kilavuz N, Delarue R, Czuczman M, Sternas L, Rose S, Beach CL, Novick S, Zhou S, Palmisano M, Li Y (2019) Population pharmacokinetics of an anti-PD-L1 antibody, durvalumab in patients with hematologic malignancies. Clin Pharmacokinet 1:5–9. https://doi.org/10.1007/s40262-019-00804-x
Baverel PG, Dubois VFS, Jin CY, Zheng Y, Song X, Jin X, Mukhopadhyay P, Gupta A, Dennis PA, Ben Y, Vicini P, Roskos L, Narwal R (2018) Population pharmacokinetics of durvalumab in cancer patients and association with longitudinal biomarkers of disease status. Clin Pharmacol Ther 103(4):631–642. https://doi.org/10.1002/cpt.982
Conflict of interest
M.J.R. reports grants from AbbVie, personal fees from Aptevo, personal fees from Cyclacel, other from BeiGene, grants from Dicerna, personal fees from multiple generic pharmaceutical companies, grants from Genentech, personal fees from Pneuma Respiratory, outside the submitted work; and Co-founder and Director, Value in Cancer Care Consortium (Vi3C, www.vi3c.org). D.A.G. declares that he has no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article refers to online published article available at https://doi.org/10.1007/s00280-019-03954-8.
About this article
Cite this article
Goldstein, D.A., Ratain, M.J. Alternative dosing regimens for atezolizumab: right dose, wrong frequency. Cancer Chemother Pharmacol 84, 1153–1155 (2019). https://doi.org/10.1007/s00280-019-03971-7