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Randomized Controlled Trial
. 2025 Feb;209(3):487-492.
doi: 10.1007/s10549-024-07555-9. Epub 2024 Dec 3.

Pexidartinib and standard neoadjuvant therapy in the adaptively randomized I-SPY2 trial for early breast cancer

Hope S Rugo  1 , Mike Campbell  2 , Christina Yau  2 , A Jo Chien  2 , Anne M Wallace  3 , Claudine Isaacs  4 , Judy C Boughey  5 , Hyo S Han  6 , Meredith Buxton  2 , Julia L Clennell  2 , Smita M Asare  7 , Katherine Steeg  2 , Amy Wilson  7 , Ruby Singhrao  2 , Jeffrey B Matthews  2 , Jane Perlmutter  8 , W Fraser Symmans  9 , Nola M Hylton  2 , Angela M DeMichele  10 , Douglas Yee  11 , Laura J Van't Veer  2 , Donald A Berry  12 , Laura J Esserman  2
Affiliations
Randomized Controlled Trial

Pexidartinib and standard neoadjuvant therapy in the adaptively randomized I-SPY2 trial for early breast cancer

Hope S Rugo et al. Breast Cancer Res Treat. 2025 Feb.

Abstract

Purpose: We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial.

Methods: I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status. The study endpoint is pathologic complete response.

Results: A total of 9 participants were randomized to receive pexidartinib with neoadjuvant paclitaxel before enrollment was halted due to a serious adverse event of vanishing bile duct syndrome. No participants received a full course of the study drug.

Conclusion: Although there remains interest in agents targeting CSF-1, hepatic toxicity appears to be a limiting factor for their use in early breast cancer.

Trial registration: NCT01042379 ( www.

Clinicaltrials: gov/ct2/show/NCT01042379 ).

Keywords: Breast cancer; Clinical trial; Colony-stimulating factor-1; Pexidartinib.

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Conflict of interest statement

Declarations. Competing interests: HS Rugo has received unrelated institutional research funding and consulting fees from Daiichi-Sankyo, Inc. C Yau receives salary and travel support from Quantum Leap Healthcare Collaborative. A Jo Chien is a member of advisory board for AstraZeneca and Genentech. C Isaacs has received publishing royalties from UpToDate and McGraw Hill. J Boughey has received publishing royalties from UpToDate and honoraria from EndoMag, PER, PeerView and OncLive. HS Han is an advisory board member for Pfizer. M Buxton maintains a leadership position at the Global Coalition for Adaptive Research. R Singhrao is a salaried employee of F. Hoffmann-La Roche. L van‘t Veer has an ownership interest and receives a salary from Agendia NV, makers of MammaPrint. D Berry DAB is an employee of, has received travel support from, is an advisor and owns stock in Berry Consultants LLC; he has received unrelated funding from Daiichi-Sankyo. L Esserman has received publishing royalties from UpToDate and Wolters Kluwer Health; she is a board member of and receives grant funding from Quantum Leap Healthcare Collaborative, the sponsor of the I-SPY2 trial; she is a member of the Blue Cross Blue Shield Medical Advisory Board.

Figures

Fig. 1
Fig. 1
Consort diagram including patients randomized to the Pexidartinib/paclitaxel and control arms
See this image and copyright information in PMC

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