Nicole O. Williams, MD, assistant professor-clinical, director, BreastCARE Program, Cancer and Aging Resiliency Clinic, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center–James, discusses the role of PI3K inhibitors in hormone receptor (HR)–positive, HER2-negative breast cancer.

Currently, PI3K inhibitors are used for the treatment of patients with HR-positive, HER2-negative breast cancer who progress on CDK4/6 inhibitors, says Williams. The PI3K inhibitor alpelisib (Piqray) was FDA-approved in May 2019 based on findings from the phase 3 SOLAR-1 trial (NCT02437318). The results demonstrated improved progression-free survival with alpelisib plus fulvestrant vs fulvestrant alone. 

Genomic testing with next-generation sequencing can be used to identify 

 mutations in patients with metastatic HR-positive, HER2-negative breast cancer, says Williams. In this patient population, approximately 40% of patients harbor these mutations, Williams adds. As such, tumor- or blood-based genomic testing can inform whether a PI3K inhibitor would be an optimal second-line treatment for a patient, concludes Williams.

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Nicole O. Williams, MD, discusses the role of PI3K inhibitors in hormone receptor–positive, HER2-negative breast cancer.  



Dr. Williams on the Role of PI3K Inhibitors in HR+/HER2- Breast Cancer

Nicole O. Williams, MD, assistant professor-clinical, director, BreastCARE Program, Cancer and Aging Resiliency Clinic, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center–James, discusses treatment considerations for selecting between CDK4/6 inhibitors in hormone receptor (HR)–positive, HER2-negative breast cancer.

Patients with HR-positive/HER2-negative disease who are started on endocrine therapy may have a CDK4/6 inhibitor added to their treatment, says Williams. Based on the findings from the MONALEESA-7 trial, ribociclib (Kisqali) should be considered for younger, premenopausal patients, Williams says. Abemaciclib (Verzenio) could be preferred for patients with central nervous system disease because some data suggest abemaciclib crosses the blood-brain barrier, Williams explains. 

Notably, the adverse effect profiles of the 3 available CDK4/6 inhibitors may inform which agent is optimal for a given patient, says Williams. Patients with pancytopenia from bone marrow involvement may tolerate abemaciclib better compared with palbociclib (Ibrance) and ribociclib, which can cause additional myelosuppression. However, abemaciclib tends to cause more gastrointestinal toxicities compared with the other agents, Williams adds. Ultimately, it is important to discuss the safety profiles of the agents with each patient, concludes Williams.

Nicole O. Williams, MD, discusses treatment considerations for selecting between CDK4/6 inhibitors in hormone receptor–positive, HER2-negative breast cancer.  



Nicole O. Williams, MD

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Dr. Williams on the Role of PI3K Inhibitors in HR+/HER2- Breast Cancer

Dr. Williams on Selecting Between CDK4/6 Inhibitors in HR+/HER2- Breast Cancer