Personalizing Adjuvant Therapy: Insights on Biomarkers, CDK4/6 Inhibitors, and Immunotherapy

In this interview, Kevin Kalinsky, MD, MS, discusses the evolving role of biomarkers, genomic assays, novel therapies, and precision medicine in early breast cancer treatment, highlighting the impact of CDK4/6 inhibitors, immunotherapy, value-based care models, and emerging research on antibody-drug conjugates, endocrine therapies, and circulating tumor DNA monitoring.

Please state your name, title, and any relevant clinical experience.

Kevin Kalinsky, MD, MS: I'm Kevin Kalinsky. I'm a professor of medicine and the division director of medical oncology at Emory University at Winship Cancer Institute.

Could you share your perspective on the role of biomarkers in guiding treatment decisions for early breast cancer?

Dr Kalinsky: We have been utilizing the estrogen receptor, progesterone receptor, and HER2 to help define the subtype of breast cancer and determine how we should be approaching patients in terms of antiestrogen therapy or anti-HER2 therapy, as well as what systemic therapy is appropriate for them to receive.

For patients with hormone receptor-positive, HER2-negative disease, we also utilize genomic assays, whether it's the 21-gene recurrence score or the 70-gene MammaPrint test, to let us know a patient’s potential risk of recurrence. We often utilize these assays, in addition to endocrine therapy, do determine whether patients might benefit from chemotherapy.

How has the integration of novel therapies, such as CDK4/6 inhibitors or immunotherapies, impacted outcomes in early breast cancer?

Dr Kalinsky: We've seen the approval of 2 CDK4/6 inhibitors, abemaciclib and ribociclib. For patients with hormone receptor-positive, HER2-negative disease, abemaciclib is approved along with endocrine therapy. Abemaciclib is approved for 2 years in patients with high-risk disease and for patients with intermediate- and high-risk disease.  Ribociclib is approved along with an aromatase inhibitor and is approved for 3 years.

Immunotherapy is approved for patients with triple-negative breast cancer and is given in the neoadjuvant setting with chemotherapy. Patients undergo surgery and then also receive a total of a full year of pembrolizumab. We've seen that there's an overall survival improvement for patients with triple-negative breast cancer if they receive immunotherapy stage II or III disease.

What are the most critical considerations when tailoring adjuvant therapy for patients with early-stage breast cancer?

Dr Kalinsky: Increasingly we're moving away from a one-size-fits-all approach. We have various treatments that have been approved, including those that I just mentioned, but there are others that are being evaluated as well, including novel endocrine therapies and antibody-drug conjugates for patients who have triple-negative breast cancer who have residual disease at the time of surgery, to see if there's a role for those drugs.

Increasingly we're focused on neither overtreating or undertreating our patients and offering precision medicine to best balance quality of life with improving outcomes.

How do you view the impact of value-based care models on treatment choices and outcomes for early breast cancer?

Dr Kalinsky: There is a continued push and pull of having drugs that have benefit for patients but don't break the bank. If there are drugs that are approved and available for patients, these are conversations that we have with patients about the risk-benefits that can be associated with a drug, and those also include financial toxicity. It is not a one-size-fits-all approach, but it is something that we need to be mindful of as our drugs get better and can be cost prohibitive.

What are you most excited about in the research pipeline for early breast cancer?

Dr Kalinsky: There remains an ongoing question about the role of antibody-drug conjugates for patients with residual disease and triple-negative breast cancer. Those drugs have been quite active and have improved survival in patients with metastatic disease. There is also a lot of interest about optimizing endocrine therapy and targeted therapies for patients with early-stage disease, including, but not limited to, novel endocrine therapies and targeted therapies.

The last thing is the potential role of monitoring with circulating tumor DNA and minimal residual disease. While there are approved platforms for patients, we don't yet know how to best utilize these assays in patients with early-stage disease. This remains an area of ongoing research and an important research question because we would like to potentially identify disease risk early and then intervene to improve the likelihood of not developing distant recurrence.