Dr. Goetz on the Use of ctDNA in the MONARCH-3 Trial in HR+/HER2- Breast Cancer

Matthew P. Goetz, MD, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses the use of circulating tumor DNA (ctDNA) in the phase III MONARCH-3 trial in hormone receptor (HR)—positive, HER2-negative breast cancer.

In a translational analysis, investigators evaluated the ctDNA of patients in the trial to see whether the somatic mutations that occur had prognostic and predictive value, says Goetz. With the Guardant360 assay, investigators found that amplification in FGFR1, cyclin D1, MYC, and EGFR were associated with poor prognosis, says Goetz. These alterations conferred a significantly worse progression-free survival with abemaciclib (Verzenio) monotherapy. Notably, in all cases, the addition of abemaciclib to letrozole or anastrozole showed a significant improvement in patient outcomes, says Goetz. These findings are important because prior studies have suggested that patients who have alterations, for example an FGFR amplification, may be resistant to CDK4/6 inhibitors, adds Goetz.

These data show that while patients with these alterations have poor outcomes to abemaciclib monotherapy, they are not altogether resistant to this therapeutic class. Rather, patients who receive CDK4/6 inhibitors in combination with an aromatase inhibitor can still derive significant benefit from the medication despite their prognosis, Goetz concludes.