Ian E. Krop, MD, PhD: The results of the KATHERINE trial had a really major impact on clinical practice, given that the effect on recurrence was so substantial and so broadly seen across subgroups and that the T-DM1 [trastuzumab emtansine] was fairly well tolerated. It was fairly easy for oncologists to recognize that this was a major advancement and should be used relatively uniformly. What was particularly interesting is that the benefits of T-DM1 over trastuzumab in the KATHERINE trial were relatively uniform. In terms of hormone receptor status and in terms of how much residual disease was there, the benefits were pretty similar. Even in patients who had pretty small amounts of residual disease—less than 1 cm, no nodal involvement at the time of surgery—those patients still had a relatively similar benefit, roughly half of the recurrence rate compared with trastuzumab. In my practice at least, I typically would use T-DM1 in the adjuvant setting for virtually any amount of invasive cancer at the time of surgery.
Sara A. Hurvitz, MD: In my opinion, KATHERINE was completely practice changing. The study was well designed because it really targeted, for enrollment, high-risk patients whose disease did not completely respond to standard very effective neoadjuvant chemotherapy, trastuzumab, and in some cases, pertuzumab. Those patients have a very high risk of having breast cancer come back as metastatic disease. The absolute improvement in invasive disease-free survival of about 11% is really extraordinary, and I think it should compel us to utilize this drug in patients who are high risk and have residual disease after standard therapy.
The tolerability of T-DM1 is actually quite good in the scheme of things when you’re comparing it with chemotherapy. Of course, the ATEMPT clinical trial compared T-DM1 with the APT trial regimen of adjuvant paclitaxel and trastuzumab, and the efficacy appeared to be pretty good. The safety, however, does indicate that T-DM1 is associated with adverse effects, and so although patients don’t feel as well in the paclitaxel-trastuzumab arm during the chemotherapy portion as they do when they’re getting T-DM1, during the maintenance trastuzumab, a woman’s quality of life goes up substantially. But in the T-DM1 arm, patients are still aware they are on a systemic chemotherapy-based regimen. Although it’s targeted chemotherapy, there are still adverse effects—fatigue, nausea, and things like this—that make a patient totally aware that they’re receiving therapy. I think it’s for that reason we saw a higher dropout rate as the trial went on in the patients who were receiving T-DM1.
Ian E. Krop, MD, PhD: I do think that the FDA expansion of the label for T-DM1 from metastatic disease to now include the postneoadjuvant setting based on the KATHERINE data was a good thing for patients. Again, the benefits of T-DM1 in this setting are really quite clear, and the balance between toxicity and efficacy is quite robust.
T-DM1 in general is fairly well tolerated, so there’s not a big cost in terms of toxicity compared with trastuzumab. The adverse effects are fairly mild. I think overall the risk-to-benefit ratio strongly favors using T-DM1 in this setting. So we were all pleased to see the FDA expand the label fairly promptly. This is the standard of care for most patients.
Transcript Edited for Clarity