A New Adjuvant Regimen for Patients with Early Breast Cancer: Interim Results

The duration and composition of adjuvant endocrine therapy continue to evolve, particularly for breast cancer patients whose disease is at high risk for recurrence. Progress has been made, especially with the addition of CDK4/6 inhibitors for patients with estrogen receptor–positive (ER+), HER2−, metastatic breast cancer. However, results in patients with early-stage breast cancer (EBC) have been less consistent, although adding abemaciclib to endocrine therapy for 2 years has significantly improved invasive disease–free survival (iDFS) in patients with nodal involvement. Researchers now report prespecified interim results with ribociclib in NATALEE, an open-label, randomized, manufacturer-sponsored, phase 3 trial involving 5101 patients with ER+/HER2− EBC (anatomical stage II/III disease).

Treatments were a nonsteroidal aromatase inhibitor (NSAI; anastrozole or letrozole) alone for 5 years or with ribociclib (dosage, 400 mg daily; 21 days on and 7 days off) for 3 years. The GnRH analog goserelin was required for gonadal suppression in men and premenopausal women. Patients with stage IIB/III disease were eligible irrespective of nodal status; those with stage IIa had at least one involved node, a grade 3 tumor, or grade 2 disease with high proliferation or high genomic risk.

More than 99% of participants were women (>50% postmenopausal). At the data cutoff (median follow-up, 34 months), 78% of combination recipients were still receiving at least one treatment. At 3 years, iDFS, the study's primary endpoint, was 90.4% in the ribociclib plus NSAI group and 87.1% in the NSAI-alone group, representing a statistically significant lower risk for an event with the addition of ribociclib. Numerically, distant DFS and overall survival also favored adding ribociclib. No new safety signals were seen with ribociclib; the most common adverse events leading to its discontinuation were liver related (~9%).