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TBCRC 006: A multicenter phase II study of neoadjuvant lapatinib and trastuzumab in patients with HER2-overexpressing breast cancer.


Sub-category:
HER2+

Category:
Breast Cancer - HER2/ER

Meeting:
2011 ASCO Annual Meeting

Abstract No:
505

Citation:
J Clin Oncol 29: 2011 (suppl; abstr 505)


Attend this session at the
ASCO Annual Meeting!
Session: Breast Cancer - HER2/ER

Type: Oral Abstract Session

Time: Sunday June 5, 9:00 AM to 12:00 PM

Location: McCormick Place Hall B1

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Author(s): J. C. N. Chang, I. A. Mayer, A. Forero-Torres, R. Nanda, M. P. Goetz, A. A. Rodriguez, A. C. Pavlick, T. Wang, S. G. Hilsenbeck, C. Gutierrez, R. Schiff, C. K. Osborne, M. F. Rimawi, on behalf of the Translational Breast Cancer Research Consortium; The Methodist Hospital Research Institute, Houston, TX; Vanderbilt-Ingram Cancer Center, Nashville, TN; University of Alabama at Birmingham, Birmingham, AL; The University of Chicago, Chicago, IL; Mayo Clinic College of Medicine, Rochester, MN; Baylor College of Medicine, Houston, TX


Abstract Disclosures


Abstract:

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.


N %
Menopausal status
Pre 32 48
Peri 4 6
Post 30 46
Age
≤50 35 53
>50 31 47
Race
White 48 73
Black 14 21
Other 4 6
Ethnicity
Hispanic 22 33
Not Hispanic 43 65
Tumor size
≤5 cm 24 39
>5 cm 38 61
Median 6 cm
ER
+ 41 62
- 25 38