Frontline Ribociclib/Letrozole Improves OS in Postmenopausal HR+ Breast Cancer, Irrespective of Metastatic Site

First-line treatment with ribociclib (Kisqali) plus letrozole improved long-term overall survival (OS) in patients with postmenopausal, hormone receptor–positive, HER2-negative advanced breast cancer, irrespective of metastatic site, number of sites, or prior (neo)adjuvant chemotherapy and endocrine therapy, according to results from an exploratory subgroup analysis of the phase 3 MONALEESA-2 study (NCT01958021) presented at the 2021 San Antonio Breast Cancer Symposium.¹

The median OS in the intention-to-treat (ITT) population who received ribociclib plus letrozole was 63.9 months compared with 51.4 months for those treated with placebo plus letrozole (HR, 0.76; 95% CI, 0.63-0.93; P = .004).

For patients with bone-only metastases, the median OS was 72.6 months with the ribociclib combination compared with 56.4 months with placebo (HR, 0.78; 95% CI, 0.50-1.21). The 5- and 6-year OS rates were 58.6% and 50.2% in the ribociclib arm vs 47.1% and 33.8% in the placebo arm, respectively. A similar benefit was observed among patients without bone-only metastases, with a median OS of 61.5 and 50.3 months in the ribociclib and placebo arms, respectively (HR, 0.77; 95% CI, 0.61-0.96). This population had 5- and 6-year OS rates of 50.6% and 42.6% in the ribociclib arm vs 43.0% and 31.5% in the placebo arm, respectively.

Although there was little difference in median OS observed among patients with liver or lung metastases who received ribociclib (37.7 months) and placebo (38.1 months), there was a late separation of curves at 5 and 6 years (HR, 0.81; 95% CI, 0.54-1.24). Additionally, the 5- and 6-year survival rates were 37.2% and 31.0% in the ribociclib arm vs 28.4% and 18.9% in the placebo arm, respectively. The median OS for patients without liver or lung metastases was 68.0 months and 56.9 months in the ribociclib and placebo arms, respectively (HR, 0.77; 95% CI, 0.62-0.97). Within this population, the 5-year and 6-year OS rates were 55.2% and 46.8% in the ribociclib cohort and 48.3% and 35.7% in the placebo cohort, respectively.

“Consistent improvement in long-term survival at 5 and 6 years with ribociclib was observed in all subgroups analyzed,” Joyce A. O’Shaughnessy, MD, chair of Breast Cancer Research and the Celebrating Women Chair in Breast Cancer at Baylor-Sammons Cancer Center, Texas Oncology, said in her presentation of the data. “MONALEESA-2, -3, and -7 have demonstrated a consistent [OS] benefit with ribociclib regardless of endocrine therapy partner, line of therapy, or menopausal status.”

The study recruited postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior therapy for advanced disease, although prior (neo)adjuvant endocrine therapy was allowed, including treatment with tamoxifen treatment.

Patients were randomized 1:1 to receive either ribociclib at 600 mg per day for 3 weeks on and 1 week off plus letrozole at 2.5 mg per day (n = 334), or placebo plus the same letrozole backbone (n = 334). A total of 668 patients were enrolled on the study. The data cutoff for this exploratory analysis was June 10, 2021.

The primary end point of the study was progression-free survival assessed locally per RECIST 1.1 criteria and the focal secondary end point was OS, which were both previously reported at the 2021 European Society for Medical Oncology Congress. Other secondary end points included overall response rate (ORR), clinical benefit rate (CBR), quality of life (QOL), and safety.

Additional findings from the study indicated that OS benefit among patients stratified by number of metastatic sites was consistent with that of the ITT population. Specifically, among patients with less than 3 metastatic sites, the median OS was 68.0 months in the ribociclib arm compared with 56.1 months in the placebo arm (HR, 0.78; 95% CI, 0.61-1.00). Moreover, the 5- and 6-year OS rates for this population were 54.8% and 47.4% in the ribociclib arm compared with 46.9% and 36.1% in the placebo arm, respectively For patients with 3 or more metastatic sites, the median OS was 55.5 months for the ribociclib arm and 46.5 months for the placebo arm (HR, 0.71; 95% CI, 0.51-0.98). Additionally, the 5- and 6-year OS for this group was 47.4% and 37.9% among those treated with ribociclib and 38.1% and 24.2% in the placebo group, respectively.

Patients who received prior treatment with (neo)adjuvant chemotherapy had a median OS of 52.0 and 44.7 months in the ribociclib and placebo arms, respectively (HR, 0.74; 95% CI, 0.56-0.98). The 5- and 6-year OS rates were 44.1% and 39.7% in the experimental arm vs 37.3% and 25.1% in the control arm, respectively. Those who did not receive prior chemotherapy had a median OS of 69.5 and 58.5 months in those respective arms (HR, 0.78; 95% CI, 0.59-1.03). The 5- and 6-year OS rates were 59.3% and 47.9% in the ribociclib arm compared with 48.9% and 37.3% in the placebo arm, respectively.

Prior endocrine therapy was divided into 3 categories. For patients who received prior treatment with a nonsteroidal aromatase inhibitor (NSAI), the median OS was 60.6 months for the ribociclib arm and 52.5 months in the placebo arm (HR, 0.63; 95% CI, 0.32-1.24). Prior treatment with tamoxifen with or without NSAI resulted in a median OS of 56.5 and 50.1 months in the ribociclib and placebo arms, respectively (HR, 0.86; 95% CI, 0.64-1.15). For patients who received no prior endocrine therapy, median OS was 68.9 months and 52.8 months, respectively (HR, 0.70; 95% CI, 0.52-0.94). The 5- and 6-year OS rates for all 3 groups among those treated with ribociclib were 53.8% and 46.1%; 45.6% and 40.3%; and 58.6% and 47.6%, respectively. Additionally, those in the placebo group had 5- and 6-year rates of 43.4% and 14.5%; 43.9% and 31.5%; and 44.0% and 35.2%, respectively.

Reference

1. O’Shaughnessy J, Stemmer SM, Burris HA, et al. Overall survival subgroup analysis by metastatic site from the phase 3 MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with advanced HR+/HER2- breast. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; Virtual. Abstract GS2-01.