Trials Examine Therapies in HER2-Positive Breast Cancer

Trastuzumab

Studies presented at the 2013 Breast Cancer Symposium, held September 7-9 in San Francisco, California, investigated the efficacy and safety of various approaches to the treatment of HER2-positive breast cancer.

An analysis of existing studies by researchers at Memorial Sloan-Kettering Cancer Center in New York City investigated the effect of adjuvant trastuzumab on locoregional recurrence in HER-2 positive breast cancer treated with postmastectomy radiation therapy.¹The researchers found that adjuvant trastuzumab significantly reduced locoregional recurrence (LRR) in women with HER2+ breast cancer who received postmastectomy radiation therapy (PMRT) but not in women who received no radiation after mastectomy.

Two cohorts of patients were compared: 139 women who received trastuzumab and 256 women who did not. To minimize lead-time bias, patient data were censored at 5 years after mastectomy in both groups.

In a subset analysis of women who received PMRT (139), trastuzumab significantly reduced LRR (7.3% no trastuzumab, 0% trastuzumab;P=.025). Among those who did not receive PMRT (256), trastuzumab did not significantly decrease LRR (6.3% no trastuzumab, 2.9 % trastuzumab;P=.28).

Also presented at the symposium was a meta-analysis of research on neoadjuvant treatments for HER2+ tumors, which found significant benefits to the addition of trastuzumab to chemotherapy and the use of dual-HER2 blockades over trastuzumab alone.²

Researchers from Massachusetts General Hospital, Harvard Medical School, and North Shore Medical Center in Massachusetts searched MEDLINE, EMBASE, and Cochrane Controlled Clinical Trials Register databases and found 36 prospective trials (N = 4130) that had at least one arm with HER2-directed therapy and reported pathologic complete response (pCR).

The addition of trastuzumab to chemotherapy did not improve the breast conserving surgery (BCS) rate (relative risk [RR] = 1.40;P=.15), but significantly increased rates of pCR (RR = 1.91;P= .0001).

Similarly, dual HER2 blockade did not improve the BCS rate compared with trastuzumab alone (RR = 1.03;P= .84), but significantly increased rates of pCR overall (RR = 1.39;P< .00001), and in both ER+ (RR= 1.72;P= .01) and ER- subsets (RR= 1.91;P= .0001), with no increase in grade 3/4 toxicity (RR = 1.13;P= .16).

Dual HER-2 blockade without chemotherapy was associated with pCR in a subset of patients (11.2% to 27%), with minimal toxicity (incidence of grade 3/4 toxicity, 1%-5%). Higher pCR was associated with improved disease-free survival (RR = 2.29;P= .006) and overall survival (RR = 4.61;P= .009).

1. Lanning RM, Riaz N, Morrow M. Effect of adjuvant trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-positive breast cancer treated with post-mastectomy radiation therapy. Presented at: 2013 Breast Cancer Symposium; September 7-9, 2013; San Francisco, CA. Abstract 61.
2. Reynolds KL, Cheng X, Bhatia A, et al. Neoadjuvant single and dual HER2 blockade among patients with localized HER2-positive breast cancer. Presented at: 2013 Breast Cancer Symposium; September 7-9, 2013; San Francisco, CA. Abstract 147.