Innovations in Breast Cancer Therapy: Key Updates and Clinical Implications

Rose DiMarco, PharmD, BCPS, BCOP, an advanced clinical pharmacist in oncology at Jefferson University Hospital's Sidney Kimmel Cancer Center in Philadelphia, Pennsylvania, discusses the crucial role of emerging breast cancer treatments in an interview with the Pharmacy Times. DiMarco shares key findings from multiple studies concerning patients with breast cancer harboring mutations, as well as highlights the need for improved inclusion of marginalized populations in these clinical trials.

Pharmacy Times: How do the significant updates in the therapeutic landscape for breast cancer discussed in your presentation compare with the previous standards of care in terms of efficacy and patient outcomes?

Rose DiMarco, PharmD, BCPS, BCOP: I would say probably the biggest update is HER-2 ultra-low [a protein that promotes growth of cancer cells] that we saw on DESTINY Breast-06 [NCT04494425]. And there's not a lot of guidance on where this is going to go, how we're going to find this in our patients, or how we're going to decide who gets treated. But I think that once those questions get answered, that is a huge game changer for patients who typically run out of options at that time. In addition, the post-MONARCH trial [NCT02107703] that we talked about, also gave us for the first-time phase 3 data that patients who progress on the CDK4/6 [cyclin-dependent kinases 4 and 6] can go get another CDK4/6 and still see benefit. It wasn't surprising that the patients that benefited the most had the most disease control on their first line of CDK4/6, but I still think really good to have this data now. And it just presents another option for patients before they have to move on to chemotherapy.

Pharmacy Times: What are the latest advancements in targeted therapies for breast cancer and how to they address genetic and molecular characteristics of different breast cancer subtypes?

DiMarco: I'll go back to DESTINY Breast-06, looking at those HER-2 ultra-low patients. That's something new that we have now that we're looking for, and something new that we're not exactly sure how to find in patients. So again, lots of questions to be answered there. But that is a huge advancement. We didn't talk about it much in our abstract, but the ESR1 [estrogen receptor 1] resistant patients who have previously received endocrine therapy [ET], there's now an option for those patients. And again, just another oral treatment before they have to move on to chemotherapy. And then also looking at things like the [sic] abstract that we talked about today are the PIK3CA [phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha] mutated patients and just giving them another option, this time in the frontline setting, are all changes from current standard care practices.

Pharmacy Times: Can you discuss the role of immunotherapy in treating breast cancer evolved in recent years and any promising immunotherapeutic agents or approaches that were highlighted in your presentation?

DiMarco: Immunotherapy right now is standard-of-care for patients with triple-negative breast cancer, especially those patients with tumors that are greater than 2 centimeters. And this would be new adjuvant chemotherapy plus pembrolizumab [Keytruda; Merck] and then pembrolizumab as maintenance after surgery. And that's kind of where immunotherapy has been living in the breast cancer space. It's also indicated for metastatic triple-negative breast cancer patients in combination with chemotherapy. But what we talk about today, is a brief abstract looking at adjuvant avelumab [Bavencio; EMD Serono Inc] which was really interesting to see. Although, and you'll end this discussion as part of our abstract, what is difficult is that the patients who would have met criteria for this trial are the same patients who are receiving that new adjuvant and adjuvant pembrolizumab. So, where does this fit? I don't know, I think where we might see this be used as in patients who we initially thought were a lower stage or a lower risk, and we find out at surgery that they actually have a more aggressive tumor. So maybe this would be an option for patients in the adjuvant setting. But right now, immunotherapy in the triple negative breast cancer space is primarily pembrolizumab.

Pharmacy Times: What are the recent developments in hormone therapies for breast cancer, particularly for hormone receptor-positive subtypes?

DiMarco: We talked about the post- MONARCH trial, which is looking at abemaciclib [Verzenio; Eli Lilly] plus fulvestrant [Faslodex; AstraZeneca] in patients who had already received a prior CDK4/6 inhibitor. So, this data is the first phase 3 data we have that shows that you can go on to a different CDK4/6 inhibitor and still see benefit. As I mentioned before, the patients who had the most benefit were, not surprisingly, patients who had better disease control on their first sign of CDK4/6, but this is finally confirmation that we can do that. I think in practice, we're already switching CDK4/6 inhibitors if patients are having difficulty tolerating a certain agent. So just having this confirmatory data has been really nice.

Pharmacy Times: What strategies are being developed to overcome resistance and improve long-term outcomes for patients?

DiMarco: It's a really difficult question, too. I think one of the biggest innovations for overcoming resistance is the ESR1-mutated agent that has just been approved, I believe last year, and that's elacestrant [Orserdu; Stemline Therapeutics, Inc], and that is specifically for patients who have developed resistance after [ET]. So, adding another agent to their tool belt really prolongs the time before patients have to start chemotherapy.

Pharmacy Times: What are the key challenges that need to be addressed to bring new treatments from research to clinical practice?

DiMarco: I think there's a lot of challenges. I think right now there's a big focus on clinical trial enrollment and diversifying the types of patients that we see in these trials, because we have a lack of knowledge and on how these agents will work in patients of marginalized populations. And I think that's one of our biggest challenges right now is to improve the recruitment strategies that we currently have for clinical trials so that we know exactly how patients of all types will respond to different treatments.