Chemotherapy, Combination Therapy Versus Trastuzumab Emtansine in HER2-positive Breast Cancer

To elevate the burden on many patients with HER2-positive breast cancer, investigators tested whether a targeted therapy of trastuzumab emtansine plus pertuzumab would lead to a safer option than traditional therapy.

In the phase 3 randomized KRISTINE study, investigators found that a combination therapy of trastuzumab emtansine (T-DM1) plus pertuzumab leads to fewer adverse effects in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings when compared to neoadjuvant trastuzumab and pertuzumab (TCHP), also known as chemotherapy. The results of this study were presented at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

Targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Furthermore, in traditional therapy, many patients struggle with quality of life due to adverse effects. In order to elevate the burden on many patients with HER2-positive breast cancer, investigators tested whether a targeted therapy of T-DM1 would lead to a safer option than traditional therapy.

“Currently, the standard of care neoadjuvant therapy for HER2-positive breast cancer is chemotherapy plus dual HER2 blockade with trastuzumab and pertuzumab, followed by HER2 blockade in the adjuvant setting, said Sara A. Hurvitz, MD, through UCLA Center for Integrative Oncology. “However, despite this, approximately 15% of patients will relapse or die within 3 to 5 years and systemic chemotherapy is associated with systemic toxicity. Therefore, effective, less toxic therapies are needed.”

Within the KRISTINE study, approximately 444 patients with HER2-positive stage 2 or 3 breast cancer aged 18 years or older were randomly assigned to receive 6 cycles of neoadjuvant T-DM1+P or neoadjuvant docetaxel, carboplatin, and TCHP. After 12 weeks following their surgery, investigators looked at event-free survival, invasive disease-free survival, overall survival, and safety. Dr Hurvitz noted that adjuvant chemotherapy was permitted for any patient in the T-DM1+P arm, but was recommended for those with residual disease in lymph nodes or in the breast.

After a follow-up of 37 months, the traditional chemotherapy treatment of TCHP had a higher event-free survival rate and achievement of pathological complete response when compared to T-DM1+P (56% vs. 44%); however, fewer patients receiving T-DM1+P had a grade 3-4 adverse effect, serious adverse effect, or adverse events leading to treatment discontinuation, according to the study.

“The similar risk of an invasive disease-free survival event with T-DM1+P and TCH+P suggests that systemic chemotherapy may be unnecessary for some patients,” said Dr Hurvitz. “This is exciting news for patients with HER2-positive breast cancer who may be looking for other treatment options.”

The authors noted that the clinical utility of systemic chemotherapy-sparing regimens needs to be confirmed. Therefore, further testing is needed.

Reference

1. Hurvitz SA, Martin M, Jung KH, et al. Neoadjuvant trastuzumab (H), pertuzumab (P), and chemotherapy versus trastuzumab emtansine (T-DM1) and P in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC): Final outcome results from the phase III KRISTINE study. J Clin Oncol 37, 2019 (suppl;abstr 500). Presented at: 2019 ASCO Annual Meeting. May 31-June 4, 2019. Chicago, Illinois.