The APHINITY Trial in Early-Stage HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH: The APHINITY trial was a randomized phase III adjuvant study that predominantly looked at patients with stage II and stage III disease, although it did include some patients with stage I HER2 [human epidermal growth factor receptor 2]–positive cancer and randomized them to receive chemotherapy with trastuzumab, with or without pertuzumab.

We have previously seen data from this trial, where there was 45 months of follow-up. At a median follow-up of about 4 years, there was a 1.7% absolute difference between the 2 arms, favoring the pertuzumab arm, and the hazard ratio was around 0.81. At that time, we had seen that the benefit of adding pertuzumab was restricted to those patients with node-positive disease as well as hormone receptor–negative disease. There was really no benefit seen in node-negative and hormone receptor–positive patients.

However, at San Antonio [Breast Cancer Symposium], they did present the updated analysis that now had 74 months of follow-up. At this point in time, the difference did seem larger than what we had seen at the 4-year follow-up time point. At 74 months of follow-up, we’re seeing about a 2.8% absolute difference between the 2 arms. We are seeing benefit that is not restricted to hormone receptor–negative patients. Now, we also see a very nice benefit within those patients with hormone receptor–positive disease. There was an absolute difference of about 3% in that group of patients, with a hazard ratio of about 0.73. Whereas in the hormone receptor–negative cohort, the hazard ratio was about 0.83. We’re seeing with longer follow-up that the hormone receptor–positive patients also gained benefit from pertuzumab.

This may be related to the timing at which hormone receptor–positive patients recur, which tends to be a little later. Now with longer follow-up, you’re seeing that benefit come out. However, the benefit was still restricted to node-positive patients. There was no benefit seen in the node-negative patients. At this point, no overall survival benefit was seen, although there was a trend toward a little benefit in the pertuzumab arm.

I think we still need to see longer follow-up from the study, to see if the survival benefit would come out. But at this time, again, what we’re seeing is a benefit from pertuzumab in node-positive patients, and we’re seeing a benefit regardless of hormone receptor status.

In my general practice, I have been adding pertuzumab for all my HER2-positive patients who are getting preoperative therapy, because I am giving preoperative therapy to all my stage II and stage III patients. In this setting I would add pertuzumab to chemotherapy and trastuzumab.

With longer follow-up from APHINITY, we have not seen any new safety signals emerge. They had continued to follow patients for potential cardiac toxicity, and the rates of cardiac toxicity were almost identical to what had been previously reported at the 4-year mark. It continues to add very minimal toxicity relative to trastuzumab alone.

Transcript edited for clarity.