The KAITLIN study is a randomised phase III trial in early stage breast cancer. The majority of patients are lymph node positive, although higher risk lymph node negative were included. It asked the question of whether substituting taxane and trastuzumab pertuzumab with TDM1 plus pertuzumab would result in, one, better efficacy and, two, decreased toxicity and patient preference. So this is a big study, about 1,800 patients. All of them got some form of anthracycline, 3-4 cycles, it could be epirubicin, doxorubicin. Then the randomisation was between paclitaxel or a taxane with trastuzumab pertuzumab, the taxane was for 3-4 cycles then it was stopped, the pertuzumab trastuzumab continued for a year, versus no taxane at all and just after the anthracycline starting with TDM1 with pertuzumab added.
The primary endpoint was invasive disease free survival and it did not meet its primary efficacy outcome. They were essentially equal so invasive disease free survival was approximately the same, very good in both arms in the mid to high nineties. So they were doing fairly well with HER2 positive breast cancer. So that was somewhat disappointing and then when we looked at the efficacy we thought that TDM, because it’s not outright chemo, might be less toxic and preferred by patients. But what was interesting was that during the chemo portion, those 3-4 cycles where the patient was on a taxane with the HER2 antibodies, the toxicity was worse in the group that got the chemo plus the HER2 antibodies. But overall grade 3/4 toxicity, serious adverse events, were fairly equal and yet a much higher dropout rate happened on the TDM1 arm.
So in general we think that paclitaxel and HER2 antibodies is more toxic than TDM1 when we use it in the metastatic setting. But when you need to continue the TDM1 for the full year versus you just get the chemo for 3-4 cycles and you stop it, that’s where you start to see that the TDM1 toxicities start to add up. So about 27% of the patients did not complete all of the TDM1 versus only about 4% who didn’t complete all of the HER2 antibodies.
So that was an interesting result and I think we learned from that. So it could be an option but actually more patients completed all their therapy if they got the full year.
One question that came up when we discussed this was if a quarter of the patients didn’t complete all of their TDM1 and you still got the same efficacy outcome, what about doing TDM1 for six months or shorter? Did we need to add the pertuzumab to the TDM1, did that account for some of the increased toxicity? So we have a lot of questions about it. It was a negative trial but we learned from it.