T-DM1 protects against invasive disease

Women with residual disease following neoadjuvant therapy for HER2-positive breast cancer have inferior long-term outcomes. Now, data from the KATHERINE trial, a phase III open-label study, reveal the superiority of the antibody–drug conjugate trastuzumab emtansine (consisting of trastuzumab conjugated to the cytotoxic microtubule inhibitor emtansine; T-DM1) in improving outcomes in this setting.

A total of 1,486 women with nonmetastatic, invasive primary breast cancer with residual disease after neoadjuvant taxane-based chemotherapy plus trastuzumab followed by surgery were randomly assigned (1:1) to receive 14 cycles, consisting of 3-weekly intravenous doses of adjuvant T-DM1 or trastuzumab. The primary end point was invasive disease-free survival (DFS).

After a median follow-up duration of >40 months in both groups, patients who received T-DM1 had a 3-year invasive DFS of 88.3% versus 77.0% in the trastuzumab group (HR 0.50, 95% CI 0.39–0.64; P < 0.001). No significant differences in overall survival were observed at this time point, although more deaths were observed among women in the trastuzumab arm (HR 0.70; 95% CI 0.47–1.05). The benefits of T-DM1 were preserved across all subgroups, including those defined by oestrogen receptor (ER) status.

Fewer women in the T-DM1 arm (71.4% versus 81.0%) completed all 14 cycles of therapy, which reflects a greater risk of grade ≥3 adverse events in this arm (25.7% versus 15.4%). The most common grade ≥3 adverse events in the T-DM1 group included reduced platelet counts (in 3.6% of patients) and peripheral sensory neuropathy (in 1.4%).

In summary, these data support the use of T-DM1 in women with residual breast cancer, owing to their higher risk of disease recurrence. Mature overall survival data from this study are eagerly awaited. The greater risk of adverse events with T-DM1 relative to trastuzumab necessitates good patient counselling about the balance between risks and benefits.


Original article

  1. von Minckwitz, G. et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N. Engl. J. Med. (2018)

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Correspondence to Peter Sidaway.

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Sidaway, P. T-DM1 protects against invasive disease. Nat Rev Clin Oncol 16, 145 (2019).

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