Potential ASCO Practice-Changers in HER2+ Breast Cancer

Kevin Kalinsky, MD, MS


July 07, 2017

I am Kevin Kalinsky, speaking from this year's annual meeting of the American Society of Clinical Oncology (ASCO 2017). I appreciate the opportunity to talk about the very important oral abstract session on the treatment of HER2-positive breast cancer that occurred at ASCO on Monday, June 5. A lot of people were abuzz about this research, and even during the session, there were heated discussions and questions as we tried to tease out the data. I will give you my impression.


The most important, highly anticipated abstract reported the data from the APHINITY trial.[1] APHINITY randomly assigned patients with early HER2-positive breast cancer to receive chemotherapy plus trastuzumab, plus 1 year of pertuzumab or placebo. Pertuzumab is approved in the metastatic setting and in the neoadjuvant setting. We have seen significant improvements in progression-free survival and overall survival in the metastatic setting, and improvements in pathologic complete response in the neoadjuvant setting. The hope with pertuzumab is that it will provide a quite robust improvement in invasive disease-free survival.

This was a positive study, with a P value of 0.045 for 3-year invasive disease-free survival (median follow-up was about 40 months). The absolute difference was about 1.1%. At 4 years, it was slightly better.

But I believe we should take a step back and consider how well the control arm is doing in that study. Around 93% of patients in the placebo arm have not had a recurrence within the 3-year follow-up, including a majority of patients who were node-positive. That is important, as we think about where we are with HER2-positive disease in the operable breast cancer setting.

I do believe that although this was a positive study, the general feeling in the room, and my takeaway as well, was that given how robust the benefits are in the metastatic setting and the neoadjuvant setting, we were hoping for more impressive improvements in what we see in the operable setting. Although this was statistically significant, I do believe the enthusiasm for this important international trial, which included almost 5000 patients, was dampened by the small and slightly incremental benefit in invasive disease-free survival. Also important to note is that the follow-up is short, and we should continue to monitor this for some time.

Ultimately, we will see whether or not these data result in an official approval for a 1-year course of pertuzumab in patients with operable HER2-positive breast cancer.

Other Notable Studies

An Italian multicenter, randomized study[2] compared giving chemotherapy with trastuzumab for a shorter duration (9 weeks) versus a longer, 1-year duration. I agree with the discussant in the session that we should be giving 1 year of trastuzumab.

The updated results for ALTTO also were presented.[3] There were really no surprises, and the results had not changed with more mature data.

The other presentation that I believe is worth mentioning is TRAIN-2,[4] the neoadjuvant trial. Participants were randomly assigned to receive trastuzumab and pertuzumab with or without an anthracycline. The pathologic complete response was quite similar between the two arms. Thus, in these patients with HER2-positive breast cancer, we may be able to withhold anthracyclines, on the basis of pathologic complete response. The HER2-targeted agents are providing such significant benefit that we realistically can use regimens that do not contain anthracyclines.

Those were some of the significant presentations in HER2-positive research this year at ASCO. The APHINITY trial has been published in the New England Journal of Medicine.[5] I imagine that we will continue to debate those data at future ASCO meetings.


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