title: Pilot neoadjuvant trial in HER2 positive breast cancer with combination of nab-paclitaxel and lapatinib.
abstract: Lapatinib, a dual kinase inhibitor against epidermal growth factor receptor (EGFR) and human epidermal receptor two (HER2) has shown efficacy in treating HER2 positive breast cancer. Nanoparticle albumin bound (nab) paclitaxel was developed to reduce toxicities from paclitaxel and improve its efficacy. Thirty patients with stage I-III HER2 positive breast cancer were treated in the neoadjuvant setting with lapatinib 1,000 mg/day and nab-paclitaxel 260 mg/m(2) every 3 weeks for four cycles. The primary end point of the trial was clinical response rate (cRR) with secondary end points including pathologic complete response rate (pCR), tolerability of the combination, and marker response. The cRR was 82.8% (24 patients) with six (20.7%) patients having complete clinical response, 18 (62.1%) having partial clinical response, and five (17.2%) stable disease. A pCR was observed in five of the 28 patients (17.9%). The most frequent grade 2 toxicities were neuropathy in nine patients (30%), fatigue in seven patients (23.3%), rash in 11 patients (36.7%), and bone pain in 10 patients (33.3%). There was no significant drop in the left ventricular ejection fraction (LVEF). Of the tissue markers examined, we were not able to find a predictor of response. The combination of lapatinib and nab-paclitaxel was well tolerated and provided good efficacy in women with HER2 positive breast cancer. This combination offers an alternative non-anthracycline-containing regimen for women with HER2 positive breast cancer.
authors.affiliation: Division of Hematology/Oncology, Northwestern University, 676 North St. Clair Street, Suite 850, Chicago, IL 60611, USA. v-kaklamani@northwestern.edu
authors.forename: Virginia G
authors.initials: VG
authors.lastname: Kaklamani
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Siziopikou
authors.forename: Denise
authors.initials: D
authors.lastname: Scholtens
authors.forename: Mario
authors.initials: M
authors.lastname: Lacouture
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.forename: Regina
authors.initials: R
authors.lastname: Uthe
authors.forename: Caitlin
authors.initials: C
authors.lastname: Meservey
authors.forename: Nora
authors.initials: N
authors.lastname: Hansen
authors.forename: Seema A
authors.initials: SA
authors.lastname: Khan
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Jeruss
authors.forename: Kevin
authors.initials: K
authors.lastname: Bethke
authors.forename: Mary
authors.initials: M
authors.lastname: Cianfrocca
authors.forename: Steven
authors.initials: S
authors.lastname: Rosen
authors.forename: Jamie
authors.initials: J
authors.lastname: Von Roenn
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wayne
authors.forename: Vamsi
authors.initials: V
authors.lastname: Parimi
authors.forename: Borko
authors.initials: B
authors.lastname: Jovanovic
authors.forename: William
authors.initials: W
authors.lastname: Gradishar
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006334:Heart Function Tests; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C520255:130-nm albumin-bound paclitaxel; C508053:ERBB2 protein, human