The standard of care for women with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer has evolved significantly in recent years as new agents and combinations have emerged that improve upon standard adjuvant and neoadjuvant treatment with trastuzumab alone. Patients with HER2-positive early breast cancer who have residual invasive disease following neoadjuvant chemotherapy and HER2-targeted therapy (eg, trastuzumab or trastuzumab plus pertuzumab) have an increased risk of recurrence and death. Trastuzumab emtansine (T-DM1), a HER2-targeting antibody drug conjugate (ADC), is an active and well-tolerated standard treatment that demonstrated a survival benefit in patients with HER2-positive metastatic breast cancer who have progressed on a prior trastuzumab-containing regimen.
During the 2018 San Antonio Breast Cancer Symposium (SABCS), a premier breast cancer conference, Charles Geyer, Jr, MD (VCU School of Medicine, Richmond, Virginia, United States), presented interim results from the randomized phase III KATHERINE trial (N = 1486), which compared adjuvant therapy with T-DM1 to adjuvant trastuzumab in patients with HER2-positive early breast cancer who had residual disease following neoadjuvant therapy including minimum six cycles of taxane-based chemotherapy and nine weeks trastuzumab. The results from this practice-changing study were simultaneously published in The New England Journal of Medicine.
At interim analysis, treatment with 14 cycles of adjuvant T-DM1 resulted in a significant improvement in rates of invasive disease-free survival (iDFS) compared to adjuvant trastuzumab. The 3-year rate of iDFS was 88.3% for patients receiving T-DM1, compared to 77.0% for patients receiving trastuzumab (HR 0.50, P<.0001). iDFS favored T-DM1 in all prespecified patient subgroups. At 3 years, a greater proportion of patients receiving T-DM1 remained free of distant recurrence (89.7% vs 83.0%; HR 0.60). There was a trend toward improved overall survival (OS) in patients receiving T-DM1, but this result was not statistically significant (HR 0.70, P = .0848).
The adverse event (AE) profile of T-DM1 was consistent with the known toxicity profile of the drug. Patients receiving T-DM1 experienced a higher rate of AEs than patients receiving trastuzumab, including a greater rate of grade ≥3 AEs (25.7% vs 15.4%) and AEs leading to treatment discontinuation (18.0% vs 2.1%). The most common AEs of any grade occurring in patients receiving T-DM1 were fatigue, nausea, platelet count decrease, liver enzyme increase, headache, arthralgia, radiation skin injury, and epistaxis.
The presenter concluded that adjuvant T-DM1 demonstrated both statistically significant and clinically meaningful improvements in iDFS compared to trastuzumab in patients with invasive residual after neoadjuvant therapy. He pointed out that these data ‘’will likely form the foundation of a new standard of care in this patient population and increase the use of neoadjuvant therapy in HER2-positive early breast cancer.’’ The discussant, Eric Winer, MD (Dana-Farber Cancer Institute, Boston, Massachusetts, United States), agreed, saying that the standard of care for early breast cancer has changed and T-DM1 should be recommended to the majority of patients with residual disease after neoadjuvant taxane-based chemotherapy and anti-HER2 therapy.