Back to Search Start Over

Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor–Positive Breast Cancer

Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor–Positive Breast Cancer

Authors :
Jane Macaskill
Alastair M. Thompson
Gemma Earl
Duncan Wheatley
Matt Trau
Patrycja Gazinska
Hannah Butler
Shah-Jalal Sarker
Timothy R. Wilson
Charles Zammit
Peter Schmid
A Shia
Louise Lim
Mark R. Lackner
Arnie Purushotham
Darren Korbie
Natalie Woodman
Sarah E Pinder
Sirwan Hadad
Paul N. Mainwaring
Peter J. Parker
Jennifer Hu
Steven Gendreau
Mika K. Derynck
Nigel J Bundred
Robert G. Price
Source :
Journal of Clinical Oncology. 34:1987-1994
Publication Year :
2016
Publisher :
American Society of Clinical Oncology (ASCO), 2016.

Abstract

Purpose Preclinical data support a key role for the PI3K pathway in estrogen receptor–positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. Patients and Methods In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment. Results There was significantly greater geometric mean Ki-67 suppression of 83.8% (one-sided 95% CI, ≥ 79.0%) for the combination and 66.0% (95% CI, ≤ 75.4%) for anastrozole (geometric mean ratio [combination:anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). PIK3CA mutations were not predictive of response to pictilisib, but there was significant interaction between response to treatment and molecular subtype (P = .03); for patients with luminal B tumors, the combination:anastrozole geometric mean ratio of Ki-67 suppression was 0.37 (95% CI, ≤ 0.67; P = .008), whereas no significant Ki-67 response was observed for pictilisib in luminal A tumors (1.01; P = .98). Multivariable analysis confirmed Ki-67 response to the combination treatment of patients with luminal B tumors irrespective of progesterone receptor status or baseline Ki-67 expression. Conclusion Adding pictilisib to anastrozole significantly increases suppression of tumor cell proliferation in luminal B primary breast cancer.

Details

ISSN :
15277755 and 0732183X
Volume :
34
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi...........cd441ce332e37b9c8523e990b04c1911
Full Text :
https://doi.org/10.1200/jco.2015.63.9179