Phase II study to evaluate the efficacy and safety of neoadjuvant lapatinib plus paclitaxel in patients with inflammatory breast cancer.
OBJECTIVE
We conducted a phase II, open-label, multicenter study to evaluate the efficacy, safety, and tolerability of daily lapatinib plus weekly paclitaxel in treatment-naïve patients with inflammatory breast cancer (IBC).


METHODS
The primary end point was pathologic complete response (pCR). Secondary end points included combined clinical response rate (based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria and clinically evaluable skin disease criteria). Patients were assigned to either cohort A (human epidermal growth factor receptor 2 [HER2] 2+ or 3+ by immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH] -amplified +/- epidermal growth factor receptor [EGFR] expression) or cohort B (HER2-negative/EGFR-positive). A subpopulation of cohort A considered HER2-positive by the current definition of overexpression (3+ by IHC or FISH-amplified) was also analyzed. Patients received lapatinib at 1,500 mg/d for 14 days, then lapatinib at 1,500 mg/d plus weekly paclitaxel (80 mg/m(2)) for 12 weeks, followed by surgical resection or additional chemotherapy.


RESULTS
Forty-nine women were enrolled (cohort A, n = 42; cohort B, n = 7). Cohort B was terminated because of slow accrual and lack of efficacy observed in IBC patients with HER2-negative/EGFR-positive tumors enrolled onto the parallel study, EGF103009. pCR occurred in 18.2% (95% CI, 5.2% to 40.3%) of cohort A patients. Combined clinical response rate was 78.6% (95% CI, 63.2% to 89.7%) in all cohort A patients and 78.1% (95% CI, 60.0% to 90.7%) in the HER2-positive subset. Common adverse events included diarrhea, rash, alopecia, and nausea (> 50% of patients in both cohorts). The incidence of grade 3 diarrhea was 55%.


CONCLUSIONS
Lapatinib monotherapy for 14 days followed by lapatinib plus paclitaxel for 12 weeks provided clinical benefit in IBC patients with HER2-overexpressing tumors without unexpected toxicity.
Boussen
Hamouda
H
Department of Medical Oncology, Institut Salah Azaiz, Tunis, Tunisia. sarroura2000@yahoo.fr
Cristofanilli
Massimo
M
Zaks
Tal
T
DeSilvio
Michelle
M
Salazar
Vanessa
V
Spector
Neil
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications; D000077341:Lapatinib; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel; D011799:Quinazolines
D011799:Quinazolines; D000077341:Lapatinib; D017239:Paclitaxel