1. Ribociclib plus letrozole provides significant overall survival benefit as compared to letrozole alone in patients with advanced breast cancer.
2. Ribociclib plus Letrozole provided a median overall survival of more than 12 months longer than Ribociclib alone.
Evidence Rating Level: 1 (Excellent)
Study Rundown: HER-2 negative disease is the most common subtype of metastatic breast cancer and is incurable. Pre-clinically, ribociclib had been shown to inhibit CDK4, a kinase that plays a key function in promoting cancer growth, and had been shown to have high drug concentrations at clinically relevant doses. However, there is a gap in knowledge as to evaluating overall survival among patients receiving first-line therapy. This study found that first-line treatment of ribociclib plus letrozole, an aromatase inhibitor, provided a significant and clinically meaningful difference in overall survival of 12.5 months compared to letrozole alone in postmenopausal patients with advanced HR-positive, HER2-negative breast cancer, with a relative reduction in risk of death by 24%. This study was limited by other trials investigating CD4/6 inhibitors as first-line therapy still undergoing reporting final overall survival and thus limit the applicability of this singular trial’s results. Nevertheless, these study’s findings are significant, as they demonstrate that ribociclib plus letrozole as first-line therapy for advanced breast cancer can provide significant overall survival benefit and decreased risk of death in these patients.
In-Depth [randomized control study]: This randomized control study followed patients who were assigned either ribociclib plus letrozole for treatment or placebo plus letrozole. Patients who were postmenopausal with locally confirmed, HR-positive, HER-2 negative recurrent or metastatic breast cancer who had not received previous systemic therapy were eligible for the study. Patients who had received previous treatment with a CDK4/6 inhibitor or any previous systemic endocrine therapy or chemotherapy were not eligible. The primary outcome was investigator-assessed progression-free survival with overall survival as the key secondary endpoint. Outcomes in the primary analysis were conducted with the Kaplan-Meier method and stratified Cox proportional-hazards model. Based on the analysis, with a median follow-up of 6.6 years, 54.2% of patients in the ribociclib group had died and 65.6% of patients in the placebo group had died. ribociclib plus Letrozole showed significant overall survival benefit as compared to placebo with letrozole, as median overall survival was 63.9 months (95% confidence interval [CI], 52.4 to 71.0) in the ribociclib group compared to 51.4 months (95% CI, 47.2 to 59.7) in the placebo group. The Kaplan-Meier estimate of overall survival at 5 years was 52.3% (95% CI, 46.5 to 57.7) in the ribociclib group compared to 43.9% (95% CI, 38.3 to 49.4) in the placebo group. Overall, this study demonstrated that ribociclib plus letrozole as compared to placebo plus letrozole provided an overall survival benefit of 12.5 months in patients with advanced HER-2 negative breast cancer.
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