The addition of ribociclib to endocrine therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer provided a statistically significant and clinically meaningful improvement in invasive disease-free survival, according to findings from the NATALEE trial presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

This update from a prespecified interim analysis was presented by lead author Dennis Slamon, MD, PhD, David Geffen School of Medicine at University of California Los Angeles.

The NATALEE trial randomized 5101 patients in a 1:1 ratio to receive adjuvant ribociclib plus endocrine therapy (letrozole or anastrozole; n = 2549) or endocrine therapy alone (n = 2552). Ribociclib was administered at 400 mg per day, 3 weeks on, 1 week off for 3 years. Letrozole was administered at 2.5 mg per day for 5 years and anastrozole at 1 mg per day for 5 years. Men and premenopausal women also received goserelin.

Patients eligible for the trial had an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1 and stage IIA, stage IIB, or stage III anatomic disease. Prior (neo)adjuvant endocrine therapy was allowed if initiated within 12 months before randomization. Patients were stratified by menopausal status, disease stage, prior (neo)adjuvant chemotherapy, and geographic region.

The prespecified interim analysis evaluating invasive disease-free survival was planned after approximately 425 invasive disease-free survival events. Reseasrchers measured invasive disease-free survival using Kaplain-Meier methods and compared statistics using stratified log-rank test.

At the data cutoff date of January 11, 2023, median follow-up was 34 months. A total of 515 (20.2%) patients completed 3 years of ribociclib and 1449 (56.8%) complete 2 years of ribociclib. Overall, 3810 (74.7%) patients remained on study treatment: 1984 receiving ribociclib plus endocrine therapy and 1826 receiving endocrine therapy alone.

After 426 events, invasive disease-free survival was evaluated with 189 events in the ribociclib arm and 237 in the endocrine therapy alone arm. Ribociclib plus endocrine therapy demonstrated significantly longer invasive disease-free survival than endocrine therapy alone (hazard ratio [HR], 0.748; 95% confidence interval [CI], 0.618 to 0.906; P = .0014). The 3-year rates of invasive disease-free survival were 90.4% vs 87.1%, respectively.

Dr Slamon and colleagues noted that ribociclib plus endocrine therapy also consistently demonstrated a trend toward improved overall survival, recurrence-free survival, and distant disease-free survival. The 3-year ribociclib treatment duration at 400 mg had a predictable safety profile that demonstrated higher favorability than the 600 mg dose used in the metastatic treatment setting.

“The NATALEE results support ribociclib [plus endocrine therapy] as the treatment of choice in a broad population of pts with stage II or III HR-positive/HER2-negative [early breast cancer],” Dr Slamon et al concluded.

Source:

Slamon DJ, Stroyakovskiy D, Yardley DA, et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2− early breast cancer: Primary results from the phase III NATALEE trial. Presented at 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract LBA500