Peter Schmid
AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (PAKT): A randomised, double-blind, placebo-controlled, phase II trial
Schmid, Peter; Abraham, Jacinta; Chan, Stephen; Wheatley, Duncan; Brunt, Murray; Nemsadze, Gia; Baird, Richard; Hee Park, Yeon; Hall, Peter; Perren, Timothy; Stein, Robert C.; László, Mangel; Ferrero, Jean-Marc; Phillips, Melissa; Conibear, John; Sarker, Shah-Jalal; Prendergast, Aaron; Cartwright, Hayley; Mousa, Kelly; Turner, Nicholas C.
Authors
Jacinta Abraham
Stephen Chan
Duncan Wheatley
Professor Adrian Brunt m.brunt@keele.ac.uk
Gia Nemsadze
Richard Baird
Yeon Hee Park
Peter Hall
Timothy Perren
Robert C. Stein
Mangel László
Jean-Marc Ferrero
Melissa Phillips
John Conibear
Shah-Jalal Sarker
Aaron Prendergast
Hayley Cartwright
Kelly Mousa
Nicholas C. Turner
Abstract
Background: The PI3K/AKT signalling pathway is frequently activated in triple-negative breast cancer (TNBC). AZD5363 is a highly-selective, oral, small molecule AKT inhibitor. The PAKT trial investigated the addition of AZD5363 to paclitaxel as 1st-line therapy for TNBC. Methods: This investigator-led, double-blind, placebo-controlled, randomised phase II trial, recruited women with previously untreated, metastatic TNBC at 42 sites in 6 countries. Patients were randomly assigned (1:1) to paclitaxel 90mg/m2 (days 1, 8, & 15) with either AZD5363 (400mg BD) or placebo (days 2-5, 9-12, 16-19) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS in the subgroup with PIK3CA/AKT1/PTEN-alterations, response, and safety. Results: Between 05/2014 and 06/2017, 140 patients were randomised to paclitaxel + AZD5363 (n = 70) or paclitaxel + placebo (n = 70). Median duration of follow-up was 18.2 months (95% CI, 13.6 to 24.0). In the ITT analysis, median PFS was 5.9 months (m) for AZD5363 compared to 4.2m for placebo (hazard ratio [HR], 0.75; 95% CI, 0.52 to 1.08; one-sided p = 0.06; two-sided p = 0.11 [predefined significance level of 0.10, one-sided]). Median OS was 19.1m for AZD5363 compared to 12.6m for placebo (HR, 0.64; 95% CI, 0.40 to 1.01; one-sided p = 0.02; two-sided p = 0.04). Results for the subgroup with PIK3CA/AKT1/PTEN-altered tumours will be presented. Most common grade 3 or worse adverse events were diarrhoea (12% [8/68] of AZD5363-treated patients vs 1% [1/70] of placebo-treated patients), infection (4% vs 1%), neutropenia (3% vs 3%), rash (4% vs 0) and fatigue (4% vs 0). Conclusions: The trial met its primary endpoint. Addition of AZD5363 to 1st-line paclitaxel therapy for TNBC resulted in significantly longer PFS and OS. AZD5363 warrants further investigation for the treatment of TNBC. Clinical trial information: NCT02423603.
Citation
Schmid, P., Abraham, J., Chan, S., Wheatley, D., Brunt, M., Nemsadze, G., …Turner, N. C. (2018, June). AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (PAKT): A randomised, double-blind, placebo-controlled, phase II trial. Presented at 2018 ASCO Annual Meeting I, Chicago, IL, USA
Conference Name | 2018 ASCO Annual Meeting I |
---|---|
Conference Location | Chicago, IL, USA |
Start Date | Jun 1, 2018 |
End Date | Jun 5, 2018 |
Acceptance Date | May 20, 2018 |
Publication Date | May 20, 2018 |
DOI | https://doi.org/10.1200/JCO.2018.36.15_suppl.1007 |
Publisher URL | https://ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.1007 |
You might also like
Hypofractionation: The standard for external beam breast irradiation
(2023)
Journal Article
Hypofractionation: The standard for external beam breast irradiation
(2023)
Journal Article
Downloadable Citations
About Keele Repository
Administrator e-mail: research.openaccess@keele.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search