Palbociclib–bazedoxifene combo for HR+/HER2− breast cancer succeeds in early trial

Treatment with the combination of palbociclib plus bazedoxifene demonstrates clinical efficacy while having an acceptable safety profile in treatment-experienced patients with hormone receptor–positive/HER2-negative (HR⁺/HER2⁻) advanced breast cancer, according to the results of a phase Ib/II study.

A total of 36 patients with HR⁺/HER2⁻ advanced breast cancer who progressed on prior endocrine therapy received bazedoxifene plus palbociclib.

The study achieved its primary efficacy endpoint, with a clinical benefit rate of 33.3 percent. Moreover, the safety profile was in line with what has previously been reported for palbociclib monotherapy.

The patients had a median progression-free survival (PFS) of 3.6 months (95 percent confidence interval [CI], 2.0–7.2). Of note, PFS was markedly shorter among patients with an activating PIK3CA mutation at baseline (hazard ratio [HR], 4.4, 95 percent CI, 1.5–13; p=0.0026); activating ESR1 mutations had a null effect on PFS.

Sixty-eight patients provided longitudinal plasma circulating tumour DNA whole-exome sequencing samples, which gave an overview of the tumour heterogeneity and the subclonal genetic evolution. This led to the identification of actionable mutations acquired during treatment.

In the treatment of HR⁺/HER2⁻ breast cancer, it is critical that patients are sensitive to endocrine therapy (ET) to obtain clinical benefit from the combination of palbociclib plus ET in HR⁺/HER2⁻ advanced breast cancer. A third-generation selective estrogen receptor (ER) modulator and selective ER degrader, bazedoxifene has exhibited antitumour activity in preclinical models of endocrine-resistant breast cancer, including those harbouring ESR1 mutations.

The present data support continued investigation of bazedoxifene in breast cancer.