A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer

Breast Cancer Res. 2018 Sep 5;20(1):109. doi: 10.1186/s13058-018-1015-x.


Background: This phase Ib study (NCT00960960) evaluated pictilisib (GDC-0941; pan-phosphatidylinositol 3-kinase inhibitor) plus paclitaxel, with and without bevacizumab or trastuzumab, or in combination with letrozole, in patients with locally recurrent or metastatic breast cancer.

Methods: This was a three-part multischedule study. Patients in parts 1 and 2, which comprised 3 + 3 dose escalation and cohort expansion stages, received pictilisib (60-330 mg) plus paclitaxel (90 mg/m2) with and without bevacizumab (10 mg/kg) or trastuzumab (2-4 mg/kg). In part 3, patients received pictilisib (260 mg) plus letrozole (2.5 mg). Primary objectives were evaluation of safety and tolerability, identification of dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of pictilisib, and recommendation of a phase II dosing regimen. Secondary endpoints included pharmacokinetics and preliminary antitumor activity.

Results: Sixty-nine patients were enrolled; all experienced at least one adverse event (AE). Grade ≥ 3 AEs, serious AEs, and AEs leading to death were reported in 50 (72.5%), 21 (30.4%), and 2 (2.9%) patients, respectively. Six (8.7%) patients reported a DLT, and the MTD and recommended phase II pictilisib doses were established where possible. There was no pictilisib-paclitaxel drug-drug interaction. Two (3.4%) patients experienced complete responses, and 17 (29.3%) patients had partial responses.

Conclusions: Combining pictilisib with paclitaxel, with and without bevacizumab or trastuzumab, or letrozole, had a manageable safety profile in patients with locally recurrent or metastatic breast cancer. The combination had antitumor activity, and the additive effect of pictilisib supported further investigation in a randomized study.

Trial registration: ClinicalTrials.gov, NCT00960960 . Registered on August 13, 2009.

Keywords: GDC-0941; PI3K; Pictilisib.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cohort Studies
  • Diarrhea / chemically induced
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Indazoles / administration & dosage
  • Indazoles / adverse effects
  • Letrozole / administration & dosage
  • Letrozole / adverse effects
  • Middle Aged
  • Nausea / chemically induced
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Trastuzumab / administration & dosage
  • Trastuzumab / adverse effects


  • 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • Indazoles
  • Sulfonamides
  • Bevacizumab
  • Letrozole
  • Trastuzumab
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT00960960