A Phase II Study Evaluating the Safety and Efficacy of Sunitinib Malate in Combination With Weekly Paclitaxel Followed by Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer.

Introduction: Neoadjuvant chemotherapy is standard treatment for locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). We hypothesized that adding sunitinib, a tyrosine kinase inhibitor with antitumor and antiangiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2-negative LABC or IBC.
Methods: We conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2-negative LABC or IBC. Patients received sunitinib 25 mg PO daily with paclitaxel 80 mg/m ² IV weekly ×12 followed by doxorubicin 24 mg/m ² IV weekly + cyclophosphamide 60 mg/m ² PO daily with G-CSF support. Response was evaluated using pCR in the breast and the CPS + EG score (clinical-pathologic scoring + estrogen receptor [ER] and grade).
Results: Seventy patients enrolled, and 66 were evaluable for efficacy. Eighteen patients (27%) had pCR in the breast (10 had ER ⁺ disease and 8 had triple-negative disease). When defining response as pCR and/or CPS + EG score ≤2, 31 (47%) were responders. In pateints with ER positive disease, 23 (64%) were responders. The most common toxicities were cytopenias and fatigue.
Conclusions: Neoadjuvant S+T followed by AC+G-CSF was safe and tolerable in LABC and IBC. The study did not meet the prespecified endpoint for pCR; however, 47% were responders using pCR and/or CPS + EG score ≤2. ER positive patients had the highest response rate (64%). The addition of sunitinib to neoadjuvant chemotherapy may provide promising incremental benefit for patients with ER positive LABC.
Competing Interests: Disclosure The following authors report they have conflicts of interest to disclose: JRG: Roche/Genentech (DSMC, Steering committee), Astra Zeneca (DSMC, consultant), Novartis (DSMC), Puma (advisory board), Immunomedics (DSMC), Radia (DSMC), Pfizer (advisory board), InBiomotion (advisory board), Sandoz/Hexal (Consultant), Genomic Health (advisory board) VG: SEngine Precision Medicine (ownership), AmunBio (Ownership), New Equilibrium Biosciences (Ownership), Seagen (Honoria/Consulting), Puma (Honoraria, Consulting), Sanofi (Honoraria/Consulting), Roche (research funding) BK: eResearch Technologies (Employer) AS: Amgen (grant funding/honoraria), AstraZeneca (consulting), Athenex (consulting) The remaining authors have no conflicts of interest to disclose.
(Copyright © 2021. Published by Elsevier Inc.)