Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 34, Issue 17, Pages 1987-+Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2015.63.9179
Keywords
-
Categories
Funding
- National Institute for Health Research and Cancer Research UK
- National Institute for Health Research Cancer Research Network
- UK Experimental Cancer Medicine Centre network
- Genentech, South San Francisco, CA
- National Breast Cancer Foundation of Australia [CG-12-07]
- National Institute for Health Research [CL-2011-04-001] Funding Source: researchfish
- The Francis Crick Institute [10130] Funding Source: researchfish
Ask authors/readers for more resources
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 geometricmean 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 geometricmean 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available