Dr Nye on Paradigm Shifts in the Management of HR+ Breast Cancer 

Lauren E. Nye, MD, breast medical oncologist, clinical medical director, Breast Cancer Prevention, the University of Kansas Cancer Center, discusses how the expansion of targeted therapies in the evolution of managing metastatic hormone receptor (HR)–-positive breast has shifted management approachescancer throughout the past decade, illustrating a significant shift from traditional treatment paradigms to a more targeted therapeutic approachin this disease space.

Historically, the treatment regimen paradigm in HR-positive breast cancer primarily consisted of endocrine therapy followed by a CDK 4/6 inhibitors and subsequent chemotherapy, Nye begins. The current treatment landscape, however, However, therapeutic approaches in this space havehas expanded beyond CDK 4/6 inhibitors to include a variety of targeted therapies and antibody-drug conjugates (ADCs) prior to the consideration of chemotherapy, she states.

The integration of tumor testing has is accordingly essential forin identifying actionable mutations and tailoring treatment plans, Nye continues. This gShe adds that genetic profiling allows for the identification of patients who would benefit fromenables the deployment of novel new agents that are sspecifically designed to target mutations induced by prior treatmentsrevious treatments. Among these are, mutations in genes such as 

-activating mutations are also a target of interest, Nye details. With the addition ofagents such asado-trastuzumab emtansine (Kadcyla) andfam-trastuzumab deruxtecan-nxki (Enhertu)to the armamentarium, other HER2-targeted ADCs are in development for patients with HR-positive and HER2-positive or HER2-low disease. have become actionable targets with available specific therapeutic options.

Nye emphasizesDespite these advancements, efforts to elucidate the optimal the need to optimize the sequencing of these agents are needed, Nye states. The challenge now lies in refining these strategies to ascertain the most beneficial treatment sequences for individual patients, taking into account the specific genetic alterations present in their tumors. This involves determining the most effective order of therapeutic application to maximize efficacy and minimize adverse effects. The ultimate goal of this approach is to enhance patient outcomes by maximizing efficacy and minimizing adverse effects, Nye emphasizes. using therapies that are not only effective but also bear lesser toxicity.

This paradigm shift reflects a broader trendin oncology towards precision medicine, which promises improved survival rates and quality of life through highly personalized treatment strategies. The challenge now lies in refining these strategies to ascertain the most beneficial treatment sequences for individual patients, taking into account the specific genetic alterations present in their tumors.

Overall, tThe treatment management of metastatic hormone receptor (HR)–-positive breast cancer has undergone profound substantial changes with the advent of targeted therapies and antibody-drug conjugates.ADCs, Nye concludes. The focus of treatment strategies for patients with this disease has shifted from a more generalized approach to an individualized highly specialized one increasingly that considers accounts for patients’ individual tumor characteristics and unique genetic profiles. The ongoing development and integration of these therapies into clinical practice underscore the dynamic nature of oncology and the continuous improvement in therapeutic options available to patients.

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Lauren E. Nye, MD, discusses how the expansion of targeted therapies in metastatic hormone receptor–positive breast cancer has shifted management approaches.

Dr Nye on Future Treatment Directions in HER2+ Breast Cancer Brain Metastases

Lauren E. Nye, MD, breast medical oncologist, clinical medical director, Breast Cancer Prevention, the University of Kansas Cancer Center, discusses future directions for the treatment of patients with HER2-positive breast cancer with brain metastases.

Dr Nye chaired an OncLive State of the Science Summit™ (SOSS) on breast cancer, during which her colleague Ryan K. Rader, MD, gave a presentation on updates in HER2-positive metastatic breast cancer. In this presentation, Rader discussed the evolving use of the antibody-drug conjugates ado-trastuzumab emtansine (T-DM1; Kadcyla) and fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in patients with HER2-positive breast cancer, as well as future directions for these therapies, Nye says.

Additionally, emerging data have shown the potential for improved treatment modalities in patients with HER2-positive disease with brain metastases, Nye explains. In cohorts 1, 2, and 3 of the phase 2 DEBBRAH trial (NCT04420598), which evaluated T-DXd in patients with HER2-positive advanced breast cancer with active brain metastases, the overall intracranial overall response rate (IC-ORR) was 46.2% (95% CI, 19.2%-74.9%). Furthermore, the single-arm, phase 2 TUXEDO-1 trial (NCT04752059), which assessed T-DXd in patients with HER2-positive breast cancer with brain metastases, showed an IC-ORR of 73.3% (95% CI, 48.1%-89.1%) in the intent-to-treat population (n = 15). This included a 13.3% complete response rate and a 60% partial response rate. In the future, more clinical trials should include patients with brain metastases to further the breast cancer field’s understanding of which agents are most effective for this disease state, Nye emphasizes.

During the SOSS, Rader also discussed the D-TORCH trial (CTRI/2021/01/030592), which investigated the use of topical 1% diclofenac (Voltaren) gel to prevent capecitabine (Xelox)-induced hand-foot syndrome in patients with breast and gynecologic cancers, Nye notes. In the breast cancer subgroup, 7.8% of patients in the diclofenac arm (n = 77) developed any-grade hand-foot syndrome vs 19.7% of those in the placebo arm (n = 71; 

 = .034). Breast oncologists are interested in implementing the D-TORCH findings in their clinical practice to prevent hand-foot syndrome in patients receiving capecitabine, Nye concludes.

Lauren E. Nye, MD, discusses future directions for the treatment of patients with HER2-positive breast cancer with brain metastases. 

Lauren Nye, MD, assistant professor, University of Kansas Medical Center, discusses neratinib (Nerlynx)-associated diarrhea in patients with HER2-positive breast cancer.

Diarrhea is a significant concern in patients who are treated with the pan-HER TKI, Nye says. These patients have likely already experienced diarrhea on previous therapy and often express concern over starting a new therapy with continued diarrhea. Physicians try to counsel patients on the importance of taking an aggressive anti—diarrheal regimen as well as explain that the diarrhea tends to be the most severe in the first 2 to 3 months of therapy before the body adapts to the drug.

The phase II CONTROL study was conducted in an effort to assess interventional strategies that could mitigate the incidence and severity of diarrhea seen in the ExteNET trial. It is important to address quality of life with regard to adverse events that occur in intervention trials, explains Nye. The CONTROL trial also indicated that the prophylactic regimen of loperamide plus colestipol had the greatest benefit in reducing the rate of diarrhea, suggesting this is what patients should be started on at the onset of neratinib therapy.

Lauren Nye, MD, assistant professor, University of Kansas Medical Center, discusses the concern of neratinib-associated diarrhea in patients with HER2-positive breast cancer.

Lauren Nye, MD

Articles

Dr Nye on Paradigm Shifts in the Management of HR+ Breast Cancer

Dr Nye on Future Treatment Directions in HER2+ Breast Cancer Brain Metastases

Dr. Nye on Neratinib-Associated Diarrhea in HER2+ Breast Cancer