Treating Early HER2+ Breast Cancer: KRISTINE

Erika P. Hamilton, MD: OK, if I got to take KATHERINE, then you get to explain KRISTINE to us.

Stephanie Graff, MD, FACP: Yes. Sara Hurvitz, MD, presented the KRISTINE trial. The KRISTINE trial is now on that other side of right-sizing of breast cancer treatments for patients with early stage disease. That study was really asking, does everybody need the chemotherapy backbone? KRISTINE randomized patients neoadjuvantly to TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab], which we’ve been talking about, versus T-DM1 [trastuzumab emtansine] in combination with pertuzumab. Now, we haven’t seen a lot of work combining T-DM1 and pertuzumab, so that’s a question and maybe a criticism of the trial. Could it have just been T-DM1? If pertuzumab had not been included, everybody would have been saying, “Well, one arm had dual HER2 blockade and the other arm didn’t.” We didn’t really see any unexpected toxicity with the addition of pertuzumab to T-DM1. I think it was a wise trial design, and the end point was pathologic complete response.

We saw that the patients who received the chemotherapy backbone had a higher pathologic complete response rate—55%. For patients who had the T-DM1 plus pertuzumab treatment, it was 44%. That was statistically different. It was considered a negative trial because the comparative nonchemotherapy arm had a lower pathologic complete response rate. But I would counter that it remains thought-provoking, because 44% of patients with early stage HER2-positive breast cancer did not need traditional chemotherapy. With an antibody-drug conjugate in combination with pertuzumab, 44% of patients had a pathologic complete response. There was a significant improvement in grade 3/4 toxicity. The antibody-drug conjugate arm had only a 13% risk of grade 3/4 toxicity compared to the chemotherapy backbone, where 64% of patients had a grade 3/4 toxicity.

The other trial that was presented and pairs nicely with it was an image-modulated approach where they were doing CT/PET [positron emission tomography] scans to assess response to neoadjuvant chemotherapy. It’s not ready for clinical practice, or it’s not ready for prime time, if you will, but they did see some nice predictive intent coming out of PET scans to determine how likely somebody was to achieve a pathologic complete response. So I can picture future directions, and I’m probably jumping ahead here, but I think that an opportunity for future directions is to consider combining those approaches. Can we give 2 cycles of T-DM1/pertuzumab and get a PET, and based on early response, add a chemotherapy backbone, or power on without the chemotherapy backbone and try to move toward those patients staying off of traditional chemotherapy when possible?

Erika P. Hamilton, MD: Yes, absolutely. One of the interesting things I thought about KRISTINE was the majority of those events that happened in the T-DM1/pertuzumab arm were actually locoregional events of the tumor not responding in the breast, etc. I agree with you. That was Dr Javier Cortés’s presentation about functional imaging, and it reminds me of the PADA-1 data, if we’re going to jump over into the ER [estrogen receptor]-positive world again, which we’re allowed to, right? I think that idea of starting the therapy and being able to figure out how a patient is doing on that in real time, and then reaching the fork in the road and potentially being able to go in 2 different directions is probably something we’re going to move toward more often. I think that’s very attractive for a patient to not guess or use these educated guesses as to what we know about their tumor, but to actually test it and see how it’s working for them, and if it’s good enough or if we need to add something in addition. If I were a patient, that would be a very attractive strategy for me.

Stephanie Graff, MD, FACP: A patient’s capacity to adapt and change and understand how the plan is unfolding is remarkable, and they are amazing. We’re doing that more and more in breast cancer. With the KATHERINE study, and even the capecitabine story in triple-negative breast cancer, there are more and more opportunities where we’re giving somebody treatment, seeing how they respond, and then deciding if we need to change the plan a little bit. I think that’s become a regular part of my communication and planning with patients, and I think that moving to an even more complicated paradigm is not something that’s going to limit us in our ability to provide best care for patients.

Transcript edited for clarity.