TBCRC 006: A multicenter phase II study of neoadjuvant lapatinib and trastuzumab in patients with HER2 overexpressing breast cancer.
505 Background: We reported that inhibition of the HER2 pathway with lapatinib (L) and trastuzumab (T) to block all homo and hetero dimer signaling leads to rapid eradication of HER2 amplified human xenografts in mice. In this clinical trial, we sought to translate these findings to patients (pts) using the L+T regimen without chemotherapy. METHODS Women with HER2+ breast cancers >3cm or >2cm with palpable lymph nodes) were eligible. Pts received weekly T (4 mg/kg loading then 2mg/kg) and daily L 1,000 mg for 12 weeks. ER+ pts also received letrozole (plus goserelin if premenopausal) to block ER/HER crosstalk. Biopsies were obtained at baseline and weeks 2, 8, and 12 (surgery) This stratified study (ER+ ER was designed to detect an increase in pathologic response rate (pRR; defined as pathologic complete response in the breast (pCR) plus residual disease that is <1 cm (npCR) from 10% with T alone to 35% in each stratum, using a Simon optimal two stage design, with one sided alpha=5% and power=85% Both strata met criteria to continue to full accrual (at least 21 per stratum) RESULTS We enrolled 66 eligible pts; 64 were evaluable for response (Table) Median tumor size was 6 cm (range 1.5 30 cm) Adverse events (AEs) were overall modest: mainly grade 1 2 (GI: 64% skin: 45% Grade 3 metabolic, GI, and liver (18% 12 pts) and grade 4 liver toxicity (1 pt) were also observed. Two pts had treatment related serious AEs (GI, liver) Efficacy results below are for the first 57 pts who had surgery as of 1/4/2011. Results from all pts will be presented at the meeting. Overall pRR was 53% (ER+ 55% ER 47% More importantly, the overall pCR rate was 28% (ER+ 21% ER 42% CONCLUSIONS L+T for 12 weeks led to a high pCR rate in pts with large HER2+ tumors without chemotherapy. Pts with npCR might be converted to pCR with longer therapy, a hypothesis to be tested in a follow up study. Our data strongly suggest that selected pts with HER2+ tumors may not need chemotherapy. [Table: see text]
Journal of clinical oncology official journal of the American Society of Clinical Oncology