A RANDOMIZED 3-WEEK PRESURGICAL TRIAL OF LAPATINIB VERSUS PLACEBO IN HER-2 POSITIVE BREAST CANCER
Menée sur 60 patientes atteintes d'un cancer du sein HER2+, cette étude randomisée évalue un traitement pré-opératoire au lapatinib pendant trois semaines
Background: Ki-67 labeling index (LI) after short-term presurgical treatment has prognostic and predictive value and may be used to screen drugs' therapeutic and preventive potential in breast cancer. Methods: We conducted a placebo-controlled trial of lapatinib, a dual EGFR and HER-2 tyrosine-kinase inhibitor, administered for 3-weeks between biopsy and surgery in 60 women with HER-2 positive breast cancer to assess its antiproliferative activity in hyperplastic, dysplastic and malignant tissue. Findings: After 3-weeks, Ki-67 LI decreased by a mean±SD of 9.3%±34.2 on lapatinib and increased by 15.1%±30.9 on placebo (p=0.007). The decrease in Ki-67 on lapatinib was greater in ER-ve tumors (-34.8% versus -12.3% in ER+ve) and in cytosol PTEN overexpressing tumors (p=0.057). The prevalence of ductal intraepithelial neoplasia in post-treatment surgical specimens was over 70%, with a median (range) Ki-67 of 15% (5-35) on lapatinib versus 20% (5-60) on placebo (p=0.06). Ductal hyperplasia was present in over 90%, with Ki-67 of 1% (1-7) on lapatinib versus 3% (1-5) on placebo (p=0.006). The median tumor diameter at surgery was 18 mm (11-57) versus 24 mm (10-37) (p=0.009). Partial response was 13.6% versus 3.7%, and tumor progression 27.3% versus 55.6% on lapatinib and placebo, respectively (p-trend=0.035), with no significant association with Ki-67 change. Interpretation: Lapatinib given for 3 weeks prior to surgery decreases cell proliferation in all compartments of field cancerization in HER-2 positive breast cancer, thus providing the rationale for a phase-III trial in HER-2 positive intraepithelial neoplasia.