Pexidartinib and Standard Neoadjuvant Therapy in the Adaptively Randomized I-SPY2 Trial for Early Breast Cancer

Authors

Hope S Rugo
Mike Campbell
Christina Yau
A Jo Chien
Anne M Wallace
Claudine Isaacs
Judy C Boughey
Hyo S Han
Meredith Buxton
Julia L Clennell
Smita M Asare
Katherine Steeg
Amy Wilson
Ruby Singhrao
Jeffrey B Matthews
Jane Perlmutter
W Fraser Symmans
Nola M Hylton
Angela M DeMichele
Douglas Yee
Laura J Van't Veer
Donald A Berry
Laura J Esserman

Publication Date

2-1-2025

Journal

Breast Cancer Research Treatment

DOI

10.1007/s10549-024-07555-9

PMID

39625569

PMCID

PMC11785665

PubMedCentral® Posted Date

12-3-2024

PubMedCentral® Full Text Version

Post-print

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

Humans, Female, Breast Neoplasms, Neoadjuvant Therapy, Antineoplastic Combined Chemotherapy Protocols, Middle Aged, Neoplasm Staging, Aminopyridines, Pyrroles, Treatment Outcome, Paclitaxel, Adult, Aged, Doxorubicin, Receptor, ErbB-2, Cyclophosphamide, Breast cancer, Clinical trial, Colony-stimulating factor-1, Pexidartinib

Published Open-Access

yes

Recommended Citation

Rugo, Hope S; Campbell, Mike; Yau, Christina; et al., "Pexidartinib and Standard Neoadjuvant Therapy in the Adaptively Randomized I-SPY2 Trial for Early Breast Cancer" (2025). Faculty, Staff and Student Publications. 4253.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4253