Defining the Role of Oral SERDs in Frontline Metastatic Breast Cancer

At the American Society of Clinical Oncology (ASCO) meeting, results from the phase III persevERA BC trial did not show a statistically significant progression-free survival (PFS) benefit with the investigational oral selective estrogen receptor degrader (SERD) giredestrant plus palbociclib (Ibrance) versus standard endocrine therapy plus palbociclib in first-line hormone receptor-positive, HER2-negative metastatic breast cancer.

In this exclusive MedPage Today video, Mabel Mardones, MD, of Rocky Mountain Cancer Centers in Denver, discusses what the findings mean for current practice and whether ESR1 mutations or other biomarkers may ultimately identify patients most likely to benefit from oral SERDs.

Following is a transcript of her remarks:

There was a prespecified boundary for efficacy defined as a hazard ratio of 0.85. And so the results showed that the investigator-assessed PFS in the combination of giredestrant, palbociclib, and placebo showed a PFS of 33 months versus 28 months in the combination of palbociclib and an aromatase inhibitor. This was a hazard ratio of 0.89, so it did not meet prespecified statistical significance.

I think that the idea here is do oral SERDs in the frontline setting in an unselected group of patients like this benefit patients? And I think what we’ve learned from this study, at least for the imminent future, is that SERDs upfront are not superior to our current standard of care. And I think this speaks a lot about, I think, the power of the CDK4/6 inhibitors. I think we were very encouraged to see yet again in a very large trial that progression-free survival in these patients are an average of 28 to 30 months. I think that’s very powerful. So it solidified our current standard of care.

I think the other thing important to note is that there are other studies that will be looking at similar populations. We await the results of an even larger study, SERENA-4 trial, that’s looking at a different SERD, camizestrant, also in a similar setting in combination with CDK4/6 inhibitors upfront. And we hope to see those results at San Antonio and we’ll see if this is another potential group for which SERDs might be important.

I think the other group that the same similar company and drug are looking into is the pionERA trial that’s looking at giredestrant and fulvestrant in the endocrine-resistant group. So I think back to groups and relevance, I think we’re hoping to understand is there a group of selected individuals — maybe those who have ESR1 mutations upfront or have other biomarkers — for which a SERD might still be important.