Phase II Study to Evaluate the Efficacy and Safety of Neoadjuvant Lapatinib Plus Paclitaxel in Patients With Inflammatory Breast Cancer

被引:49
作者
Boussen, Hamouda [1 ]
Cristofanilli, Massimo
Zaks, Tal
DeSilvio, Michelle
Salazar, Vanessa
Spector, Neil
机构
[1] Inst Salah Azaiz, Dept Med Oncol, Tunis 1006, Tunisia
关键词
TYROSINE KINASE INHIBITOR; GROWTH-FACTOR; TRASTUZUMAB; SURVIVAL; GW572016; HER-2; CAPECITABINE; EXPRESSION; DOCETAXEL; CISPLATIN;
D O I
10.1200/JCO.2009.21.8594
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose We conducted a phase II, open-label, multicenter study to evaluate the efficacy, safety, and tolerability of daily lapatinib plus weekly paclitaxel in treatment-naive patients with inflammatory breast cancer (IBC). Patients and 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%. Conclusion 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.
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收藏
页码:3248 / 3255
页数:8
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