Future Breast Cancer Treatments: A Focus on SIRDs, Biomarkers

Mabel Mardones, MD, board-certified medical oncologist and hematologist with an advanced subspecialty in breast cancer at Rocky Mountain Cancer Centers, led a discussion on new treatments for HR+/HER2– breast cancer at the Denver Regional Institute for Value-Based Medicine^®.

Mardones highlighted in an interview with The American Journal of Managed Care® the growing issue of drug resistance in HR+/HER2– breast cancer. She emphasized the need for biomarkers to identify patients who could benefit from more aggressive therapies, such as triplet therapy. She also discussed the promising potential of selective estrogen receptor degraders (SIRDs), which may replace aromatase inhibitors as the standard of care due to their superior efficacy and reduced side effects.

This transcript was lightly edited for clarity.

Transcript

How are researchers addressing the challenges of drug resistance and recurrence in HR+/HER2- breast cancer?

With the inavolisib approval, there's the concept that, obviously, many patients are, in fact, endocrine-resistant and will become endocrine-resistant. This is not likely early on in the course of their treatment, but likely somewhere around years 5 through 10 or beyond. These are patients who metastasize and are resistant to an aromatase inhibitor.

I think that being forward thinkers and thinking ahead of the menu of choices we already have and using biomarkers like this trial did. The PIK3CA patients that progress on aromatase inhibitors within a year are the patients that are going to get a triplet therapy, so escalate therapy in those [patients] who are truly endocrine resistant.

There are a lot of challenges in sequencing that still remain today that I think are not answered. I think we have a lot of choices out but then we're left with "How do we choose one agent over another?" I think that speaks to the testament of how quickly the FDA is approving these agents, the clinical trials, and how robust they have been, but that leaves us in the clinic with challenges. I think biomarkers probably would be my conclusion statement on how to do a better job with resistance.

In your opinion, what are the most exciting areas of research that may lead to significant breakthroughs in the treatment of HR+/HER2- breast cancer in the next decade?

We have a variety of menus in our current treatment options with the oral SIRDs, selective estrogen receptor degraders. I tell my patients this; we've made it known that SIRDs are superior to our most potent injection, which is faslodex [fulvestrant] in the metastatic setting. There's no reason to believe that SIRDS are not going to be more effective than an aromatase inhibitor.

If we look at just the trajectory of how tamoxifen beat aromatase inhibitors, now we have this new wave of options. I do think that SIRDs will replace aromatase inhibitors probably in the next 10 years, whether that's only in the high-risk population or not is to be determined.

But these are the trials that are now being done in high-risk women and in high-risk women who are switching from an aromatase inhibitor to a SIRD after 2 to 5 years.

Those trials are accruing; they're about to be enrolling in the community, patients who truly represent the patients that we're treating and will be treating ongoingly, and women are incredibly excited to have choices.

I think probably the biggest thing or selling point of these SIRDs is the fact that arthralgias and joint pain, which seems to be probably the top-line concern and number one reason for discontinuation of aromatase inhibitors, is a whole lot less—that we've noted so far. That's been encouraging, and we remain optimistic that, hopefully, the compliance level of adjuvant endocrine therapy will rise as we bring on better choices but less toxic choices as well.