Schmid, P, Abraham, J, Chan, S, Wheatley, D, Brunt, M, Nemsadze, G, Baird, R, Park, YH, Hall, P, Perren, T, Stein, RC, Laszlo, M, Ferrero, J-M, Phillips, M, Conibear, J, Sarker, S-J, Prendergast, A, Cartwrightx, H, Mousa, K and Turner, NC (2018) 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. In: 2018 ASCO Annual Meeting I, 01-05 Jun 2018.

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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.

Item Type: Conference or Workshop Item (Speech)
Additional Information: The final version of this article/speech can be found online with all relevant information at the following; This material on this page is ©2018 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RM Therapeutics. Pharmacology > Physical medicine. Physical therapy. Including massage, exercise, occupational therapy, hydrotherapy, phototherapy, radiotherapy, thermotherapy, electrotherapy
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
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Depositing User: Symplectic
Date Deposited: 13 Aug 2021 10:37
Last Modified: 13 Aug 2021 10:37

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