Two Noteworthy Studies of Preventive Treatment in Early-Stage HER2-Positive Breast Cancer: APHINITY and ATEMPT

In patients with early-stage breast cancer who have undergone surgery, the purpose of the treatments we administer after the operation is to reduce the likelihood of disease recurrence. In oncology, this is called adjuvant treatment . The likelihood of disease recurrence varies according to the characteristics of the patient and the tumor. San Antonio Breast Cancer Symposiumpresented many new studies in this area. Let us look at two studies evaluating adjuvant treatment in HER2-positive early-stage breast cancer: The first study APHINITY (BIG 4-11) was a study evaluating the effectiveness of adding to the standard treatment used in our early-stage HER2-positive patients, namely the combination of trastuzumab (Herceptin) and chemotherapy, pertuzumab (Perjeta) . The 6-year results of this study were published. A total of 4805 patients were enrolled. This study showed that adding pertuzumab to the standard treatment of trastuzumab-chemotherapy contributed only overall survival 1% to overall survival (94.8% versus 93.9% in those not receiving it). Pertuzumab contributed disease-free survival 3% to disease-free survival. In subgroup evaluations, an additional benefit of 4.5% (87.9% versus 83.4%) was demonstrated in patients whose disease had spread to the axillary lymph nodes, and an additional benefit of 3% in hormone receptor-positive patients. No significant difference in side effects was found between the two groups. As is known, our standard approach is to use pertuzumab together with chemotherapy and trastuzumab in patients with HER2-positive metastatic breast cancer and before surgery in patients with locally advanced disease. Considering its benefit and cost, adding pertuzumab to preventive treatment in early-stage disease appears to have no place. We believe that administering these treatments before surgery from the outset would be a better option for patients found to have axillary involvement after surgery. The second study in this area compared, as preventive treatment in patients with early-stage disease, trastuzumab emtansine (T-DM1, Kadcyla) with the combination of paclitaxel and trastuzumab: ATEMPT . The study enrolled patients who had undergone surgery for early-stage tumors smaller than 3 cm without axillary involvement, a total of 497 patients. For these stage 1, HER2-positive patients, the 7-year follow-up results were announced. Their 7-year disease-free survival (DFS), in those using T-DM1, was observed to be an additional 4% better (97.5% versus 93.2), while recurrence-free survival was 99%. Although side effect rates were similar in the two patient groups, among the patients receiving T-DM1, 11% had to discontinue the drug because of drug-related side effects. According to this study, recommending T-DM1 as preventive treatment in early-stage HER2-positive disease is not appropriate. The study results did not describe in detail long-term side effects such as hair loss and effects on ovarian function that patients might experience. These also need to be evaluated in detail in the article to be published.

Summary of Both Studies

Patients with early-stage disease have very good survival and a low likelihood of recurrence. While we are trying to move toward approaches that reduce treatment for this group of patients, it is unclear how much benefit adding more drugs will provide. Until a subgroup shown to benefit is identified, in particular, chemotherapy-trastuzumab will remain our standard approach in early-stage HER2-positive breast cancer.

• In the figure below, you can see the mechanisms of action of all these targeted drugs approved for use in our country in HER2-positive breast cancer.