The addition of ribociclib to letrozole prolonged overall survival (OS) across multiple subgroups compared with placebo and letrozole among postmenopausal patients with hormone receptor (HR)-positive and HER2-negative advanced breast cancer, according to a prespecified exploratory subgroup analysis of the MONALEESA-2 trial presented at the 2021 San Antonio Breast Cancer Symposium (SABCS).

“Consistent improvement in long-term survival at 5 and 6 years with ribociclib was observed in all subgroups analyzed,” Joyce O’Shaughnessy, MD, of the Texas Oncology-Baylor University Medical Center and The US Oncology Research Network in Dallas, Texas, and lead author of the study, said.

The randomized, phase 3 MONALEESA-2 trial evaluated the first-line treatment of postmenopausal patients with HR-positive, HER2-negative advanced breast cancer with letrozole plus ribociclib or placebo. The results demonstrated significantly longer OS with ribociclib compared with placebo in the intention-to-treat population (hazard ratio [HR], 0.76; 95% CI, 0.63-0.93; P =.004). The present prespecified analysis is of 668 patients within subgroups of special interest, but was exploratory and not powered for significance testing.

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The OS benefit with the addition of ribociclib to letrozole was consistent across subgroups, including number of metastases and metastatic sites.

Patients with less than 3 metastatic sites demonstrated a median OS of 68.0 and 56.1 months with ribociclib or placebo, respectively, which translated to a 6-year rate of 47.7% and 36.1%, respectively (HR, 0.78; 95% CI, 0.61-1.00). Survival was lower overall for patients with 3 or more metastatic sites, but ribociclib significantly prolonged survival compared with placebo, with a median of 55.5 or 46.5 months, respectively (HR, 0.71; 95% CI, 0.51-0.98). The 6-year OS was 37.9% with ribociclib and 24.2% with placebo.

The OS benefit was similar among patients with or without bone-only metastases as the intention-to-treat (ITT) population. For patients with only bone metastases, ribociclib resulted in a median OS of 72.6 months compared with 56.4 months with placebo (HR, 0.78; 95% CI, 0.50-1.21) and 50.2% and 33.8% OS, respectively, at 6 years. For patients without bone metastases, the median OS was 61.5 and 50.3 months, respectively, and a 6-year rate of 42.6% and 31.5%, respectively (HR, 0.77; 95% CI, 0.61-0.96).

Patients with liver metastases also benefit from the addition of ribociclib, with a 6-year OS of 31.0% compared with 18.9% with placebo. However, there was a late separation of the survival curve, Dr O’Shaughnessy noted, which resulted in a similar median OS of 37.7 and 38.1 months, respectively (HR, 0.81; 95% CI, 0.54-1.24). For patients without liver metastases, the median OS was 68.0 months with ribociclib and 56.9 months with placebo (HR, 0.77; 95% CI, 0.62-0.97) and a rate of 46.8% and 35.7%, respectively, at 6 years.

Prior chemotherapy did not affect the benefit of ribociclib, as the OS benefit was similar to the ITT population regardless of prior chemotherapy. For patients who received prior chemotherapy, the median OS was 52.0 and 44.7 months with ribociclib or placebo, respectively (HR, 0.74; 95% CI, 0.6-0.98) and a 6-year rate of 39.7% or 25.1%, respectively. In the subgroup that did not receive prior chemotherapy, the median OS was 69.5 months with ribociclib and 58.5 months with placebo (HR, 0.78; 95% CI, 0.59-1.03). The 6-year OS was 47.9% and 37.3% with ribociclib or placebo, respectively.

The OS benefit among patients who received prior endocrine therapy was less clear, and Dr O’Shaughnessy noted that the sample size was small for patients who had previously received an aromatase inhibitor.

Dr O’Shaughnessy concluded that, “this exploratory subgroup analysis demonstrates improved survival benefit with first-line ribociclib plus letrozole compared with placebo plus letrozole in postmenopausal patients with HR-positive/HER2-negative advanced breast cancer in the MONALEESA-2 trial.”

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


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 cancer. Presented at SABCS 2021; December 7-10, 2021; San Antonio, TX. Abstract GS2-01.

This article originally appeared on Cancer Therapy Advisor