T-DM1 Shows 'Striking' Benefit for HER2+ Breast Cancer With Residual Invasive Disease

Lidia Schapira, MD


March 07, 2019

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

von Minckwitz G, Huang CS, Mano MS, et al
N Engl J Med. 2019;380:617-628.

Study Summary

This phase 3, open-label trial included patients with HER2-positive early breast cancer who had residual invasive disease in the breast or axilla at surgery after having previously received neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Previous studies have shown that patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus HER2-targeted therapy have a worse prognosis than those who have no residual cancer.

Patients were randomly assigned to receive adjuvant trastuzumab emtansine (T-DM1) or trastuzumab for 14 cycles. T-DM1 is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1) and has demonstrated a benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.

The primary endpoint was invasive disease-free survival. Among those who received T-DM1, there were 91 events (invasive disease or death) compared with 165 in the trastuzumab group. The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39-0.64; P < .001).

Although there were more adverse events associated with T-DM1 than with trastuzumab alone, the safety data in the trial were consistent with the established safety profile of T-DM1.

The authors concluded that the risk for invasive breast cancer recurrence or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone in HER2-positive early breast cancer patients with residual invasive disease after completion of neoadjuvant therapy.


These results were presented at the 2018 San Antonio Breast Cancer Symposium (SABCS), with a simultaneous publication in New England Journal of Medicine.

This is the kind of study that requires no interpretation. Results are clear and the obvious advantage in favor of adjuvant T-DM1 is striking.

One question that may come to mind is whether trastuzumab alone is considered a standard of care in the area of double anti-HER2 therapy. At SABCS, this was addressed by Charles Geyer, Jr, MD, the senior author on this manuscript. While he acknowledged that pertuzumab is becoming increasingly used in the adjuvant setting, particularly for those patients who received the doublet preoperatively, he felt that the magnitude of benefit observed in the T-DM1 group is sufficiently robust to make this a more effective and attractive option.

It is also worth pointing out that the benefit was consistent across several subgroups and the safety profile was acceptable. Oncologists who are familiar with and have experience using T-DM1 in the metastatic setting may agree that it is generally well tolerated. We look forward to learning more from trials currently underway to characterize the benefit of T-DM1 in the neoadjuvant and adjuvant settings.


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