The addition of pictilisib, a PI3K inhibitor, to anastrozole significantly improved suppression of tumor cell proliferation in luminal B primary breast cancer, a study published in the Journal of Clinical Oncology has shown.1

Because preclinical data have suggested that combining PI3K inhibitors with endocrine therapy may overcome resistance to endocrine therapy in estrogen receptor (ER)-positive breast cancer, researchers sought to evaluate whether adding pictilisib to anastrozole can increase the antitumor effects of endocrine therapy in primary breast cancer. Investigators also aimed to identify the most appropriate patient population for combination therapy.

For the open-label, phase 2 trial, researchers enrolled 75 postmenopausal women with newly diagnosed operable ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Participants were randomly assigned 2:1 to receive 2 weeks of preoperative treatment with anastrozole 1 mg once daily plus pictilisib 260 mg once daily, or anastrozole alone.

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Results showed that geometric mean Ki-67 suppression was 83.8% with the combination and 66.0% with anastrozole alone (geometric mean ratio [combination:anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). Ki-67 protein suppression was a marker for the inhibition of tumor cell proliferation.

Researchers found that 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). In contrast, investigators observed no significant Ki-67 response for pictilisib in luminal A tumors (geometric mean ratio, 1.01; P = .98).

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The study further demonstrated that Ki-67 response to combination therapy in patients with luminal B tumors occurred regardless of progesterone receptor status or baseline Ki-67 expression.


  1. Schmid P, Pinder SE, Wheatley D, et al. 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 [published online ahead of print March 14, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.63.9179.