Adjuvant Therapy for Early-Stage HER2-Positive Breast Cancer - Episode 11
Mohammad Jahanzeb, MD: So, at this ASCO, we have results of a large randomized trial, PERSEPHONE, with more than 4000 patients comparing 6 months with 12 months, and that has shown noninferiority of 2 months, which really puts a wrinkle in our decision making because previously we had shown that 2 years is no better than 1 year. We settled for 1 year after the PHARE study presented by Dr. Xavier Pivot, which also had more than 3000 patients. It could not meet the noninferiority of 6 months, so 12 months remained the standard. Now we have to go back into debate and discussion about optimal duration of therapy in those patients.
Then if we keep increasing the risk and not talk about patients with larger tumors or a number of positive lymph nodes, that’s the subset that had shown benefit in the APHINITY trial from adding pertuzumab to trastuzumab, both given for 12 months in that setting. And there was not benefit in low-risk patients. So, even though the absolute benefit was small, we tend to offer doublet therapy in patients with high risk.
Another data set came from the ExteNET trial, where patients who had completed 12 months of adjuvant trastuzumab were offered neratinib versus placebo, and we saw in that trial that the overall result was positive for disease-free survival at the 5-year follow-up mark. But subset analysis by surface markers showed only hormone receptor—positive patients to benefit from that therapy.
So, now we have to take 2 separate data sets and see how we can combine them. And there’s not any clear answer to that, and there are no plans to take an APHINITY-type approach followed by a neratinib-type approach. We have to take these data sets separately and maybe have a discussion of our uncertainties about these separate data sets with patients at the very highest risk with a lot of positive nodes.
Transcript Edited for Clarity