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Optimizing Tx of HRpos HER2neg MBC

CME

Optimizing Treatment for Patients With HR-Positive/HER2-Negative MBC

Physicians: Maximum of 0.50 AMA PRA Category 1 Credit™

Released: March 24, 2025

Expiration: September 23, 2025

Sara A. Hurvitz
Sara A. Hurvitz, MD, FACP
CME/CE Information

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Personal Perspective, Clinical Insights, and Overall Conclusions

When talking to a patient about the various treatment options available for the frontline management of HR-positive, HER2-negative MBC, it is important to consider the efficacy data as well as the patient's preexisting comorbidities, concomitant medications, and goals of care. It is also important to go through the nuances of the way different trials were designed that led to the FDA approval of various treatment options. For example, patients whose disease recurred during or within 12 months since the completion of adjuvant AI are eligible to receive different therapies compared with patients who experienced disease progression greater than 12 months after completing adjuvant AI therapy or a patient who developed de novo MBC that is completely treatment-naive. 

In my clinical practice, the most important features that I evaluate outside of the patient’s recent use of adjuvant ET are concomitant medications and comorbidities that may place them at a higher risk of side effects. For example, the risk of developing QTc prolongation should be carefully considered before prescribing ribociclib. Any prior history of VTE could place a patient at a higher risk of another VTE event with abemaciclib. Preexisting lung disease may place the patient at a higher risk of developing ILD/pnuemonitis with the use of any of the 3 CDK4/6 inhibitors. A prior history of hyperglycemia may place the patient at a higher risk of developing hyperglycemia if the patient is placed on a PI3 kinase pathway inhibitor such as inavolisib, alpelisib, or capivasertib. 

In summary, we are in an era where we have multiple treatment options available for our patients with newly diagnosed HR-positive, HER2-negative MBC. It is critical that we consider multiple factors when helping patients make a decision regarding which initial therapy is optimal for them. When starting a patient on therapy, it is important to involve a multidisciplinary team that includes advanced practice providers, pharmacists, and sometimes subspecialists such as endocrinologists, cardiologists, and gastroenterologists to assist with the proactive management of side effects that may occur. Ultimately, selecting among the 3 available CDK4/6 inhibitors should depend not only on efficacy but also on the patient's comorbid conditions, concomitant medications, goals of care, and wishes.

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