Clinical Cases in HER2+ Breast Cancer - Episode 6

Case 1: Adjuvant Therapy After pCR in Early Stage HER2+ Breast Cancer 

Ruta Rao, MD: Let’s talk about a similar patient who originally had node-positive disease, but this patient achieves a pathologic complete response [pCR] after neoadjuvant treatment. She could get the same neoadjuvant treatment that we talked about already. What would you do in this case in terms of adjuvant therapy decision-making?

Sara Tolaney, MD, MPH: We know that, for a patient who has residual disease, we should give T-DM1 [trastuzumab emtansine] based on the KATHERINE study. In someone who achieves a pCR, we do not have any data to suggest that we need to escalate therapy. In fact, the recommendation would be to continue HER2 [human epidermal growth factor receptor 2]–directed therapy in the adjuvant setting. The area of controversy that comes up is about if you give trastuzumab and pertuzumab to someone who achieves a pCR to dual HER2-based therapy, or should you give trastuzumab alone? The challenge is that we don’t have a trial that has adequately addressed this question, so we don’t have a study that randomized patients with a pCR to HP [trastuzumab, pertuzumab] or H [trastuzumab] after preoperative HP [trastuzumab, pertuzumab]–based treatment.

Our data come with long-term outcomes from the APHINITY trial, which was an adjuvant study, so it wasn’t adapted based on preoperative therapy, in which we have long-term outcomes for patients who had gotten a year of HP [trastuzumab, pertuzumab]. That data look compelling and suggest that there’s good benefit from HP [trastuzumab, pertuzumab] treatment. However, there was no benefit in the node-negative population from HP [trastuzumab, pertuzumab]. If you had a node-negative patient, this is where the controversy comes up even more. One would argue about whether you need to give the pertuzumab. It becomes complicated because you didn’t know if the patient was node-negative prior to your preoperative treatment. You could have had treatment effect in that node.

My personal preference has been regardless of nodal status. For anyone who is getting preoperative therapy, I have given HP [trastuzumab, pertuzumab]–based therapy. We know it improves pCR, and it could potentially have an impact on local therapy options. It can have long-term treatment benefit in those patients, particularly with node-positive disease. I then continue the HP [trastuzumab, pertuzumab] out back if they got a pCR. I understand that we may be overtreating some patients, particularly those node-negative patients who are likely not deriving long-term benefit from pertuzumab, but it is challenging to tease out which patients you could omit pertuzumab from. One could also argue that the patient developed a pCR to the pertuzumab-based therapy and were likely deriving benefit, so I end up continuing it out back. We don’t have the answer for whom we could omit pertuzumab from in someone who achieves pCR.

Ruta Rao, MD: I follow along exactly as you said. For patients who achieve a pCR, I also give HP [trastuzumab, pertuzumab] to finish the year for the same reasons you just stated. What about you, Dr Jhaveri?

Komal Jhaveri, MD, FACP: I completely concur. Rarely, we’ll have a patient who might struggle with toxicity based on their nodal status. As Dr Tolaney was pointing out, if she was node-negative and knowing what we know from the APHINITY data, then perhaps that’s the patient population that did not derive a disease-free survival benefit. We discussed getting rid of the pertuzumab and completing the trastuzumab-based option, but those are rare patients. Most patients tolerate HP [trastuzumab, pertuzumab]–based chemotherapy out back very well and complete the year, so I do the same, acknowledging that we might be overtreating.

Transcript edited for clarity.