Novel Approaches for Stage I HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH: For those patients who have stage I HER2 [human epidermal growth factor receptor 2]–positive disease, they are still at an increased risk of recurrence compared with patients who have HER2-negative breast cancers. Some retrospective series suggest that these patients have a risk of recurrence that ranges somewhere between 10% and 30%. The challenge had been that these patients had been excluded from the pivotal adjuvant studies. For example, they were not included in the NCCTG-N9831 and NSABP B-31 trials and were predominantly excluded from BCIRG 006.

We really didn’t have data to help us decide what to do with these patients. The APT trial looked at giving less chemotherapy to these patients. It really looked to see if giving a year of paclitaxel and trastuzumab was associated with a clinically acceptable event rate. With 7 years of follow-up, that trial has shown that the regimen is associated with a 7-year recurrence-free interval of 97.5%. This really demonstrates that very few patients with stage I HER2-positive cancers will recur after giving the TH [docetaxel, trastuzumab] regimen.

The more recently presented trial, the ATEMPT trial, looked to see if we could potentially de-escalate therapy even further. This trial looked to see if we could give a year of T-DM1 [trastuzumab emtansine] instead of giving the TH [docetaxel, trastuzumab] regimen, and it looked to see if the year of T-DM1 [trastuzumab emtansine] was associated with a clinically acceptable disease-free survival. The trial also compared toxicities between T-DM1 [trastuzumab emtansine] and TH [docetaxel, trastuzumab]. With 3 years of follow-up, the trial demonstrated that a year of T-DM1 [trastuzumab emtansine] was associated with about a 98% 3-year disease-free survival. Only 2 patients in the trial of the 375 on the T-DM1 [trastuzumab emtansine] arm had metastatic recurrence. There were very few events in that arm, in general. However, when the trial then compared rates of clinically relevant toxicities between a year of T-DM1 [trastuzumab emtansine] and the TH [docetaxel, trastuzumab] regimen, it found that the rates of clinically relevant toxicities were actually identical in the 2 arms—46% in each arm.

While the studies suggest that T-DM1 [trastuzumab emtansine] is associated with a very good event rate and would be a very reasonable treatment regimen, technically it did not show that it had fewer toxicities than TH [docetaxel, trastuzumab]. However, it’s important to note that when looking at patient-reported outcomes, we did see that quality of life was actually better in those patients receiving T-DM1 [trastuzumab emtansine] compared with TH [docetaxel, trastuzumab]. There was less hair loss and less neurotoxicity.

There are differences in toxicities between T-DM1 [trastuzumab emtansine] and TH [docetaxel, trastuzumab], and it’s important to factor those toxicities in when making decisions for your patients who have stage I HER2-positive cancers. For example, if you have a patient who has underlying neuropathy, you might want to consider a year of T-DM1 [trastuzumab emtansine] versus TH [docetaxel, trastuzumab]. But we have to acknowledge that 17% of patients didn’t complete a year of T-DM1 [trastuzumab emtansine] because of toxicities.

This is very similar to what we saw in KATHERINE. Those patients, at time of onset of toxicity, went on to receive trastuzumab. If we are giving T-DM1 [trastuzumab emtansine] to our stage I HER2-positive patients, and they run into challenges with toxicity, we do need to think about shifting them to trastuzumab to complete their year of treatment.

Transcript edited for clarity.