FINALLY! results of NO CHEMO neoadjuvant trial of herceptin+tykerb+AI+/- LHRH agonist

[Lani]

in other words--Drs. Schiff and Osbourne mice trials performed in humans


© 2013 by American Society of Clinical Oncology

Multicenter Phase II Study of Neoadjuvant Lapatinib and Trastuzumab With Hormonal Therapy and Without Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: TBCRC 006

Mothaffar F. Rimawi⇑,
Ingrid A. Mayer,
Andres Forero,
Rita Nanda,
Matthew P. Goetz,
Angel A. Rodriguez,
Anne C. Pavlick,
Tao Wang,
Susan G. Hilsenbeck,
Carolina Gutierrez,
Rachel Schiff,
C. Kent Osborne and
Jenny C. Chang

+ Author Affiliations

Mothaffar F. Rimawi, Angel A. Rodriguez, Anne C. Pavlick, Tao Wang, Susan G. Hilsenbeck, Carolina Gutierrez, Rachel Schiff, C. Kent Osborne, and Jenny C. Chang, Baylor College of Medicine, Houston, TX; Ingrid A. Mayer, Vanderbilt-Ingram Cancer Center, Nashville, TN; Andres Forero, University of Alabama at Birmingham, Birmingham, AL; Rita Nanda, Mayo Clinic College of Medicine, Rochester, MN; and Matthew P. Goetz, University of Chicago, Chicago, IL.

Corresponding author: Mothaffar F. Rimwai, MD, Baylor College of Medicine, One Baylor Plaza, Breast Center, BCM 660, Houston, TX 77030; e-mail: rimawi@bcm.edu.

C.K.O. and J.C.C. contributed equally to this work.

Abstract

Purpose We previously reported the eradication of human epidermal growth factor receptor 2 (HER2)– amplified human xenografts in mice by inhibition of the HER2 pathway with lapatinib and trastuzumab to block all homo- and heterodimer signaling as well as by blockade of estrogen receptor (ER) when expressed. In this clinical trial, we sought to translate these findings to patients using targeted therapy without chemotherapy.

Patients and Methods Women with stages II to III HER2-positive breast cancers were eligible. They received trastuzumab once per week (4 mg/kg loading, then 2 mg/kg) and lapatinib 1000 mg once per day for 12 weeks. Women with ER-positive tumors also received letrozole (plus a luteinizing hormone–releasing hormone [LHRH] agonist if premenopausal). Pathologic response was assessed by ER status. Biopsies were obtained at baseline, weeks 2 and 8, and time of surgery.

Results Sixty-six patients were enrolled, and 64 were eligible and evaluable for response. Median tumor size was 6 cm (range, 1.5 to 30 cm). Adverse events were mainly grades 1 to 2 (GI, 63%; skin, 46%). Grade 3 metabolic, GI, and liver (18%; 12 patients) and grade 4 liver toxicities (one patient) were also observed. Overall, in-breast pathologic complete response (pCR; ypT0-is) was 27% (ER positive, 21%; ER negative, 36%). The rate of low-volume residual disease (ypT1a-b) was 22% (ER positive, 33%; ER negative, 4%).

Conclusion In patients with locally advanced HER2-positive breast cancer, our approach of targeted therapy only resulted in a high pCR rate without chemotherapy. Our data support the hypothesis that selected patients with HER2-positive tumors may not need chemotherapy, and more-complete blockade of HER receptors and ER is an effective strategy worthy of further study.
Footnotes

See accompanying editorial on page 1703 and article on page 1719

Written on behalf of the Translational Breast Cancer Research Consortium (TBCRC).