ASCO 2023: Adding a CDK4/6 Inhibitor to Endocrine Therapy for Early-Stage Breast Cancer

By: Julia Fiederlein Cipriano
Posted: Friday, June 2, 2023

According to Dennis J. Slamon, MD, of the University of California, Los Angeles, and colleagues, the addition of the CDK4/6 inhibitor ribociclib to standard-of-care endocrine therapy appeared to significantly improve invasive disease–free survival outcomes in patients with hormone receptor–positive, HER2-negative early-stage breast cancer. Results from an interim analysis of the phase III NATALEE trial, which were presented during a press briefing before the 2023 American Society for Clinical Oncology (ASCO) Annual Meeting (Abstract LBA500), also support this well-tolerated combination as the adjuvant treatment of choice in those with N0 disease. 

A total of 5,101 men and premenopausal or postmenopausal women with stage IIA (either N0 with additional risk factors or N1), IIB, or III disease were randomly assigned in a 1:1 ratio to receive endocrine therapy (letrozole: 2.5 mg/day; or anastrozole: 1.0 mg/day) for at least 5 years with or without ribociclib (400 mg/day, 3 weeks on/1 week off) for 3 years. Men and premenopausal women were also treated with goserelin. Follow-up data were provided for a median of 34 months.

“[An] extended duration of treatment is crucial to prolong cell-cycle arrest and drive more tumor cells into senescence or death,” the investigators explained. “[Thus, this] 3-year duration of treatment with ribociclib at a dose of 400 mg was chosen to improve tolerability while maintaining efficacy.”

The duration of invasive disease–free survival seemed to be significantly prolonged with the combination treatment versus endocrine therapy alone (hazard ratio = 0.748; P = .0014); the 3-year rates were 90.4% and 87.1%, respectively. According to the investigators, the invasive disease–free survival benefit was generally consistent across stratification factors and other subgroups. Overall, recurrence-free, and distant disease–free survival outcomes appeared to consistently favor the combination treatment. The administered dose of ribociclib was found to demonstrate a favorable safety profile with no new signals, according to the investigators.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2023 ASCO Annual Meeting

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