title: Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP Foundation FB-6, a phase II study.
abstract: This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m(2) on days 1, 8, and 15 every 28 days for four cycles concurrently with pazopanib 800 mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6 months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA-C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17 % (16/93). The pCR rate was 9 % (6/67) in hormone receptor-positive tumors and 38 % (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39 % of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27 %), diarrhea (5 %), ALT and AST elevations (each 5 %), and hypertension (5 %). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA, USA, Antoinette.Tan@CarolinasHealthCare.org.
authors.forename: A R
authors.initials: AR
authors.lastname: Tan
authors.forename: H
authors.initials: H
authors.lastname: Johannes
authors.forename: P
authors.initials: P
authors.lastname: Rastogi
authors.forename: S A
authors.initials: SA
authors.lastname: Jacobs
authors.forename: A
authors.initials: A
authors.lastname: Robidoux
authors.forename: P J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: M P
authors.initials: MP
authors.lastname: Thirlwell
authors.forename: L
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: P J
authors.initials: PJ
authors.lastname: Stella
authors.forename: R
authors.initials: R
authors.lastname: Goel
authors.forename: T B
authors.initials: TB
authors.lastname: Julian
authors.forename: L
authors.initials: L
authors.lastname: Provencher
authors.forename: M J
authors.initials: MJ
authors.lastname: Bury
authors.forename: K
authors.initials: K
authors.lastname: Bhatt
authors.forename: C E
authors.initials: CE
authors.lastname: Geyer
authors.forename: S M
authors.initials: SM
authors.lastname: Swain
authors.forename: E P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: N
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007191:Indazoles; D008198:Lymph Nodes / Q000187:drug effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D003520:Cyclophosphamide; D004317:Doxorubicin; D005472:Fluorouracil; D007191:Indazoles; D017239:Paclitaxel; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; D013449:Sulfonamides; C516667:pazopanib