Breast Cancer Coverage from Every Angle

Ribociclib Plus Fulvestrant With or Without PI3K Inhibitor in Advanced Breast Cancer

By: Kayci Reyer
Posted: Monday, December 14, 2020

According to findings published in Clinical Cancer Research, a combination treatment containing the CDK4/6 inhibitor ribociclib may be safe for patients with hormone receptor–positive, HER2-negative advanced breast cancer unless combined with a PI3K inhibitor. Professor Soo Chin Lee, of the National University Hospital in Singapore, and colleagues found a doublet regimen of ribociclib plus fulvestrant demonstrated tolerability. In contrast, triplet regimens with the PI3K inhibitors alpelisib or buparlisib resulted in unacceptable toxicities and are not recommended in this setting.

The phase Ib study included 70 women with hormone receptor–positive, HER2-negative advanced breast cancer in menopause and who had experienced disease progression following aromatase inhibitor treatment. Patients were assigned to receive one of four treatment regimens: continuous dosing of ribociclib plus fulvestrant, cyclic dosing of ribociclib plus fulvestrant, ribociclib plus alpelisib plus fulvestrant, or ribociclib plus buparlisib plus fulvestrant. The recommended phase II dose of cyclic ribociclib was 600 mg versus 400 mg for continuous ribociclib, plus 500 mg of fulvestrant for patients undergoing a doublet regimen. The recommended phase II doses for those receiving a triplet regimen including buparlisib were 400 mg of ribociclib, 30 mg of buparlisib, and 500 mg of fulvestrant. The recommended phase II doses for the alpelisib triplet combination were not found due to the early discontinuation of this regimen caused by unexpected toxicity.

Patients receiving the triplet regimen, including buparlisib, experienced a 25% overall response rate, the highest among the study groups. Both doublet combinations had safety profiles consistent with findings from prior studies. The exposure of neither alpelisib nor buparlisib was affected by the varying ribociclib doses.

Disclosure: For full disclosures of the study authors, visit

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