BACKGROUND: Approximately 40% of hormone receptor-positive, HER2-negative breast 
cancers (BCs) are associated with activating mutations of the 
phosphatidylinositol 3-kinase (PI3K) pathway. Pictilisib, a potent and highly 
specific class I pan-PI3K inhibitor, demonstrated preclinical activity in BC 
cell lines and may potentiate the effect of taxanes, benefiting patients with or 
without aberrant activation of the PI3K pathway. PEGGY (NCT01740336), a 
randomised, placebo-controlled phase II trial, examined whether pictilisib 
augments the anti-tumour activity of paclitaxel in patients with hormone 
receptor-positive, HER2-negative locally recurrent or metastatic BC (mBC). We 
report results from the protocol-specified interim analysis.
PATIENTS AND METHODS: One hundred and eighty-three eligible patients were 
randomised (1:1) to receive paclitaxel (90 mg/m2 weekly for 3 weeks in every 
28-day cycle) with either 260 mg pictilisib or placebo (daily on days 1-5 every 
week). The primary end point was progression-free survival (PFS) in the 
intention-to-treat (ITT) population and patients with PIK3CA-mutated tumours. 
Secondary end points included overall response rate (ORR), duration of response, 
and safety.
RESULTS: In the ITT population, the median PFS was 8.2 months with pictilisib (n 
= 91) versus 7.8 months with placebo (n = 92) [hazard ratio (HR) for progression 
or death, 0.95; 95% confidence interval (CI) 0.62-1.46; P = 0.83]. In patients 
with PIK3CA-mutated tumours, the median PFS was 7.3 months for pictilisib (n = 
32) versus 5.8 months with placebo (n = 30) (HR, 1.06; 95% CI 0.52-2.12; P = 
0.88). ORR was similar between treatment arms. The safety profile of pictilisib 
was consistent with previous reports, with no new safety signals. Proportions of 
patients with grade ≥3 adverse events (AEs), serious AEs, and dose 
reductions/discontinuations due to AEs were higher with pictilisib.
CONCLUSIONS: PEGGY did not meet its primary end point, revealing no significant 
benefit from adding pictilisib to paclitaxel for patients with hormone 
receptor-positive, HER2-negative locally recurrent or mBC.
CLINICAL TRIAL NUMBER: NCT01740336.