Avoiding Chemotherapy in HER2-Positive Breast Cancer
Dual targeting of human epidermal growth factor receptor 2 produced in-breast pathologic complete remission in 27% of patients.
The goal of avoiding chemotherapy and its attendant adverse effects is attractive to breast cancer patients and clinicians. In appropriate patients with estrogen receptor (ER)-positive breast cancer, the strategy of exhausting endocrine therapy options has been used to delay time to chemotherapy and help maintain quality of life. A similar strategy has been considered in select patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Previous reports have shown that combining anti-HER2 agents with endocrine agents in ER-positive and HER2-positive metastatic breast cancer is more effective than endocrine therapy alone.
More recently, a clinical trial involving women with HER2-positive disease compared various combinations of chemotherapy and anti-HER2 treatment administered preoperatively, including one that combined pertuzumab and trastuzumab without chemotherapy (Lancet Oncol 2012 Jan; 13:25). Although the pathologic complete remission (pCR) rate was higher with chemotherapy, patients who received only the antibodies still attained a pCR rate of nearly 20%, suggesting that chemotherapy may be avoided in certain patients.
To test such a no-chemotherapy approach further, investigators conducted a multicenter, phase II trial involving 66 patients with stage II–III HER2-positive disease (62% were ER-positive) who received standard trastuzumab plus lapatinib (1000 mg daily) for 12 weeks. Women with ER-positive tumors also received letrozole (plus a luteinizing hormone–releasing hormone agonist, if premenopausal). Sequential biopsies were obtained at diagnosis, at weeks 2 and 8, and at surgery. The median tumor size was 6 cm (range, 1–30 cm).
Overall, the in-breast pCR was 27% (21% for ER-positive disease; 36% for ER-negative disease). The most common adverse effects were those largely expected with lapatinib: diarrhea (grades 1–2, 63%; grades 3–4, 3%), rash (grades 1–2, 55%; grades 3–4, 1%), fatigue (32%), nausea (31%), and elevated liver function tests (grades 1–2, 18%; grade 3, 5%; grade 4, 2%).
CITATION(S):
Rimawi M et al. 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 J Clin Oncol 2013 May 10; 31:1726.
