Transcript

I'm Dr Julie Gralow. I'm the Director of Breast Medical Oncology at the Seattle Cancer Care Alliance, and the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington. I'll be discussing some abstracts that will be presented at the ASCO 2020 virtual scientific meeting.

The KAITLIN trial is an interesting trial in early stage of HER2-positive breast cancer, looking at if there are potentially more efficacious and less toxic ways of treating this group of patients. In KAITLIN, the majority of patients were lymph node-positive, HER2-positive, but there were lymph node-negative patients who had higher risk who were accrued.

All patients got anthracycline chemotherapy for 3 to 4 cycles. It was the anthracycline regimen of the investigators' choice, either epirubicin or doxorubicin. Patients were randomized to either three to four cycles of a taxane, with a full year of trastuzumab and pertuzumab.

That's the standard of care arm versus an experimental arm, where after the anthracycline the patient's got T-DM1, the antibody-drug conjugate, along with pertuzumab for a full year. The hope was that the T-DM1 with pertuzumab regimen could possibly be better, and also that it might be more tolerable for patients.

What we saw in about 1800 patients randomized at lots of sites across the world, was that the two regiments were the same in terms of the primary end point, which was invasive disease-free survival. Patients were doing well. There aren't a lot of invasive recurrences happening, but it was not different between the two arms.

What was maybe a little bit of a surprise was that the T-DM1/pertuzumab arm, more patients dropped off and discontinued that, that was supposed to go on for a whole year. Even though technically, grade three, four, or five toxicities were about the same in each arm and serious adverse events were about the same, more people dropped off of the T-DM1 and pertuzumab, and couldn't complete a whole year.

That was about 27 percent of patients. Over a quarter of patients dropped off. Now they could go on and get trastuzumab, pertuzumab instead, but only about 4% of patients did not complete the full year of the two antibodies, the trastuzumab and the pertuzumab.

We tend to think when we use T-DM1 in the metastatic setting, that it's more tolerable than a taxane with HER2 antibodies. That is true. As long as you're continuing the chemotherapy, the regimen with the chemotherapy does have a lot of toxicity. In this study, patients only got 3 to 4 cycles of the taxane and then it stopped.

The bulk of the time they were on their HER2 directed therapy, they were just getting the HER2 antibodies or T-DM1 in pertuzumab. That's where we started to see that the side effects of T-DM1 do start to show up, and outweigh just giving the HER2 antibodies, trastuzumab and pertuzumab alone.

I think we learned from that we did not see that it was more efficacious. It was an equally efficacious regimen. There may be patients who benefit from one versus another or prefer one versus another, but I think it won't change standard of care because of the high dropout rate in trying to complete the full year of T-DM1 in the adjuvant setting.