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Breast Cancer Research
Published in: Breast Cancer Research 1/2018

Open Access 01-12-2018 | Research article

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

Authors: Patrick Schöffski, Sara Cresta, Ingrid A. Mayer, Hans Wildiers, Silvia Damian, Steven Gendreau, Isabelle Rooney, Kari M. Morrissey, Jill M. Spoerke, Vivian W. Ng, Stina M. Singel, Eric Winer

Published in: Breast Cancer Research | Issue 1/2018

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Abstract

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.
Appendix
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Metadata
Title
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
Authors
Patrick Schöffski
Sara Cresta
Ingrid A. Mayer
Hans Wildiers
Silvia Damian
Steven Gendreau
Isabelle Rooney
Kari M. Morrissey
Jill M. Spoerke
Vivian W. Ng
Stina M. Singel
Eric Winer
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2018
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-018-1015-x

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