Time-to-Event Analysis of Polatuzumab Vedotin-Induced Peripheral Neuropathy to Assist in the Comparison of Clinical Dosing Regimens.

Autor: Lu D; Genentech Inc., South San Francisco, California, USA., Gillespie WR; Metrum Research Group LLC, Tariffville, Connecticut, USA., Girish S; Genentech Inc., South San Francisco, California, USA., Agarwal P; Genentech Inc., South San Francisco, California, USA., Li C; Genentech Inc., South San Francisco, California, USA., Hirata J; Genentech Inc., South San Francisco, California, USA., Chu YW; Genentech Inc., South San Francisco, California, USA., Kagedal M; Genentech Inc., South San Francisco, California, USA., Leon L; Genentech Inc., South San Francisco, California, USA., Maiya V; Genentech Inc., South San Francisco, California, USA., Jin JY; Genentech Inc., South San Francisco, California, USA.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2017 Jun; Vol. 6 (6), pp. 401-408. Date of Electronic Publication: 2017 May 23.
DOI: 10.1002/psp4.12192
Abstrakt: Polatuzumab vedotin, an antibody-drug conjugate containing monomethyl auristatin E, was associated with an incidence of grade ≥2 peripheral neuropathy (PN) of 55-72% in patients with indolent non-Hodgkin lymphoma in a phase II study, when dosed 1.8-2.4 mg/kg every 3 weeks until progression or for a maximum of 17 cycles. To quantify the correlation of conjugate exposure and treatment duration with PN risk, a time-to-event model was developed using data from phase I and II studies. The model suggested that PN risk increased with conjugate exposure and treatment cycles, and a trend for increased risk with body weight and albumin concentration. When capping the treatment duration to six to eight cycles, the risk ratio of a dose of 2.4 mg/kg vs. 1.8 mg/kg was ≥1.29; the predicted incidence of grade ≥2 PN at 1.8-2.4 mg/kg dose levels was 17.8-37.2%, which is comparable with other antimicrotubule agents for lymphoma treatment.
(© 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
Externí odkaz: