The PRIME II Study in HR+ Breast Cancer

Sara Hurvitz, MD: Andrew, I’m going to ask you to shift away now from our expertise collectively on this panel, from systemic therapy, and let’s talk about another important paper that was presented at the San Antonio Breast Cancer Symposium relating to the use of radiation therapy or not in selected patients. Can you take us through the PRIME 2 clinical trial?

Andrew Seidman, MD: Yes. I’ll put on my radiation oncologist’s hat for this one. Just to give some historical context, the theme of this study is to identify patients who can safely omit whole breast radiation after breast-conserving surgery for their ER-positive, HER2-negative breast cancer. The CALGB 9343 study, reported by Kevin Hughes, MD, about a decade ago, was a similar study and was about half the size of the PRIME 2 study.

That study enrolled women who were 70 years of age and older. The adjuvant endocrine therapy in that trial was tamoxifen only. The definition for margin status used in that trial was basically no tumor on ink, and these were largely patients with T1 tumors. There were 2% who had T2 tumors. At the end of the day, while whole breast radiotherapy reduced locoregional recurrence, there was no overall survival benefit. I think we learned that these are patients who are largely dying of things other than breast cancer in any case. So, overall survival and breast cancer-specific survival were not affected, which was good news because you can now select patients with clear margins who are over age 70 who could safely forego radiotherapy, understanding that they have a higher risk of ipsilateral breast tumor recurrence.

The PRIME 2 study involved 1326 patients randomized to adjuvant endocrine therapy—more contemporary endocrine therapy, not just tamoxifen alone—with or without whole breast radiotherapy. The mean age in this study was 71, and these were pretty small tumors. Forty percent were T1a and b, half were T1c, 10% had T2 tumors, only 3% had grade 3 tumors, and only 3% had lymphovascular invasion.

The results were quite similar to the CALGB study, in that there was better local control now at 10 years. The initial report published in The Lancet Oncology 5 years ago was now more mature. There was a 9 percentage point reduction from 99% to 90% difference in local recurrence, but again no difference in overall survival, as one might expect. For me, I don’t know if these are practice changing as much as practice confirming data, that you can certainly identify patients who can safely forego radiotherapy. In this trial they required a 1 mm margin. That was one other difference.

Sara Hurvitz, MD: Great. Yes, that was a great description of the evidence. Well done radiation oncologist, Andrew.

Andrew Seidman, MD: Thank you.

Sara Hurvitz, MD: I do think it is nice for our patients, and we’re in an era now where we’re looking for ways to de-escalate therapy, and so for a very well-defined subgroup, especially those with strong ER expression, because I think the study showed that those with low ER expression, if you’re talking about somebody with a 5%, 10% ER expression, maybe this wouldn’t be the appropriate decision to make here.

Transcript edited for clarity.