PEGGY: A phase II randomised study of the PI3-kinase (PI3K) inhibitor pictilisib (GDC-0941) plus paclitaxel in patients (pts) with hormone receptor (HR)-positive, HER2-negative locally recurrent or metastatic breast cancer (mBC)

Background: Increased activity of the PI3K pathway promotes proliferation and invasion of cancer cells; at least one-third of HR-positive, HER2-negative BCs are associated with PI3K pathway-activating mutations. Pre-clinical data suggest that the potent and highly specific class I PI3K inhibitor pictilisib may potentiate the effect of taxanes and benefit patients with or without aberrant activation of the PI3K pathway. PEGGY (NCT01740336) is a multicentre, randomised, placebo (pla)-controlled phase II trial designed to test whether pictilisib augments the anti-tumour activity of paclitaxel in pts with HR-positive, HER2-negative locally recurrent or mBC. Here we report results from the protocol-specified planned interim analysis.

Materials and Methods: Overall, 183 eligible pts not previously treated with intravenous chemotherapy for mBC were randomised 1:1 to receive paclitaxel (90mg/m² weekly for 3 out of 4 weeks in every 28-day cycle) with either 260mg pictilisib or pla (daily on Days 1–5 every week). The primary endpoint was progression-free survival (PFS) in the intention-to-treat (ITT) population and in pts with PIK3CA mutations. Secondary endpoints included overall response rate (ORR), duration of response and safety. Adverse events (AEs) were reported according to NCI-CTCAE V4. Safety analyses were based on patients who received at least one dose of study drug and by actual treatment received.

Results: Median PFS in the ITT population was 8.2 months with pictilisib (n=91) and 7.8 months with pla (n=92) (HR for progression or death, 0.95; 95%CI 0.62–1.46; P=0.83). In pts with PIK3CA mutations, median PFS was 7.3 months with pictilisib (n=32, 35.2%) and 5.8 months with pla (n=30, 32.6%) (HR 1.06; 95%CI 0.52–2.12; P=0.88). ORR was similar with pictilisib or pla (22% and 20%, respectively). Median pictilisib/pla treatment duration in the ITT population was 5.4 months with pictilisib (range 0–16) and 5.8 months (0–15) with pla, while median pictilisib/pla dose intensities were 91.7% (range 23–105) and 98.6% (41–103), respectively. Proportions of grade ≥3 AEs, serious AEs (SAEs) and dose reductions/discontinuations due to AEs were higher with pictilisib than with pla (table). The safety profile of pictilisib was consistent with previous reports, with no new safety signals.

Conclusion: PEGGY did not meet its primary endpoint in either the ITT or PIK3CA-mutant populations and revealed no significant benefit from adding pictilisib to paclitaxel for pts with HR-positive, HER2-negative locally recurrent or mBC.

Conflict of interest: Advisory Board: MH: Advisory Board Roche Belgium on Avastin. Corporate-sponsored Research: LF: Roche. Other Substantive Relationships: DA, SS and JZ: Employee of Genentech Inc.