Breast Cancer Coverage from Every Angle

Ribociclib-Based Therapy for Advanced Breast Cancer Under Study

By: Joshua Swore
Posted: Monday, June 14, 2021

Results of the phase I/II TRINITI-1 trial, published in Clinical Cancer Research, suggested the safety and efficacy of exemestane, ribociclib, and everolimus in patients with advanced hormone receptor (HR)-positive/HER2-negative breast cancer. According to Stacy Moulder-Thompson, MD, of The University of Texas MD Anderson Cancer Center, and colleagues, “These results suggest that continued CDK4/6 blockade with ribociclib and targeting of the PI3K/AKT/mTOR signaling pathway may be a promising approach in patients with HR+/HER2− advanced breast cancer who have progressed on a CDK4/6 inhibitor.”

The open-label, single-arm study included 104 patients with HR+/HER2– breast cancer. Phase I of the study (17 patients) focused on maximum dose tolerance. Phase II (95 patients) targeted patients who experienced disease progression on a CDK4/6 inhibitor.

The authors reported that the maximum tolerated dose was not reached. However, a dose dependent drug-to-drug interaction was observed between ribociclib and everolimus by pharmacokinetic analysis. This resulted in an everolimus trough concentration two- to fivefold higher than expected. The researchers recommended phase II daily doses of ribociclib at 300 mg, everolimus at 2.5 mg, and exemestane at 25 mg for group I and ribociclib at 200 mg, everolimus at 5 mg, and exemestane at 25 mg in group II. The clinical benefit rate at 24 weeks was 41.1%, which exceeded the predetermined threshold of 10%.

The group reported ten deaths, seven of which were from disease progression. Safety analysis found that the most common hematologic adverse event was neutropenia, with 69.2% of patients experiencing the event and 51% at grade 3 or 4. The most common nonhematologic adverse event was stomatitis, which occurred in 40.4% of patients, with 2.9% at grade 3 or 4. The researchers did not find any new safety signals or grade 3 or 4 QTc prolongation.

Disclosure: For full disclosures of the study authors visit,

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