Top

Published in:

01-12-2019 | NSCLC | Editorial

Alternative dosing regimens for atezolizumab: right dose, wrong frequency

Authors: Daniel A. Goldstein, Mark J. Ratain

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2019

Abstract

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.

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRef

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRef

10.

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 CrossRefPubMedPubMedCentral

Title: Alternative dosing regimens for atezolizumab: right dose, wrong frequency
Authors: Daniel A. Goldstein
Mark J. Ratain
Publication date: 01-12-2019
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
Pharmacokinetics
NSCLC
Bevacizumab
Urothelial Cancer
Urothelial Cancer
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03971-7

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2019

Skin platinum deposition in colorectal cancer patients following oxaliplatin-based therapy

Endothelial nitric oxide synthase c.-813C>T predicts for proteinuria in metastatic breast cancer patients treated with bevacizumab-based chemotherapy

Upregulation of miR-519 enhances radiosensitivity of esophageal squamous cell carcinoma trough targeting PI3K/AKT/mTOR signaling pathway

A phase I delayed-start, randomized and pharmacodynamic study of metformin and chemotherapy in patients with solid tumors

Correction to: Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine and Oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial

BATF2 inhibits chemotherapy resistance by suppressing AP-1 in vincristine-resistant gastric cancer cells

Keynote webinar | Spotlight on antibody–drug conjugates in cancer