1. Overall survival was longer in the group receiving ribociclib with letrozole as compared with the placebo group
2. Severe adverse events, especially neutropenia, are more prevalent in the ribociclib group compared to the placebo group
Evidence Rating Level: 1 (Excellent)
Study Rundown: This study aimed to compare the overall survival (OS) of postmenopausal women with hormone receptor (HR)-positive, HER2-negative recurrent or metastatic breast cancer receiving either ribociclib-letrozole or placebo-letrozole combinations. Additionally, the safety profile of ribociclib-letrozole was reported. The OS was longer in the group receiving ribociclib with letrozole as compared with the placebo group (63.9 months vs. 51.4 months, respectively). As well, Kaplan-Meier survival curves showed greater OS at 48, 60, and 72 months for the ribociclib group as compared to the placebo group (60.9% vs. 55.2%, 52.3% vs. 43.9%, 44.2% vs. 32.0%, respectively). The most common severe adverse effect (AE) was neutropenia and more patients taking ribociclib experienced this than those on placebo. Other less common, but severe AEs, included hepatobiliary toxic effects and prolonged QT interval, both of which were more prevalent in the ribociclib group. However, there were no new safety signals reported during this study. Limitations to this study include the under-representation of Black patients (2.5% of the trial participants) as the majority of patients recruited were from Europe and North America. As such, the results from this study must be interpreted with that in mind. Overall, the addition of ribociclib to letrozole increased the overall survival of postmenopausal female patients with HR-positive, HER2-negative recurrent or metastatic breast cancer as compared to placebo with letrozole.
Click to read the study in The New England Journal of Medicine
Relevant Reading: Treating cancer with selective CDK4/6 inhibitors
In-Depth [randomized controlled trial]: This phase 3 randomized controlled trial randomly assigned 668 postmenopausal female patients with HR-positive, HER2-negative recurrent or metastatic breast cancer on a 1:1 basis to receive either ribociclib with letrozole or placebo with letrozole. Patients who had previously received CDK4/6 inhibitors or previous systemic endocrine or chemo-therapy were ineligible. Group allocation was blinded to all involved. The median overall survival was greater in the ribociclib-letrozole group at 63.9 months, compared to the placebo-letrozole group at 51.4 months (hazard ratio (HR), 0.76; 95% confidence interval (CI), 0.63 to 0.93). The estimate of OS by Kaplan-Meier curves at 60 months was less in the placebo group at 43.9% (95% CI, 38.3% to 49.4%) compared to the ribociclib group at 52.3% (95% CI, 46.5% to 57.7%). At 72 months, the Kaplan-Meier curves showed OS at 44.2% for the ribociclib group (95% CI, 38.5% to 49.8%) compared to 32.0% for the placebo group (95% CI, 26.8% to 37.3%). Neutropenia was the most common severe AE and patients on ribociclib were affected more so than those on placebo (63.8% vs. 1.2%). Other severe AEs that were more common in the ribociclib group include hepatobiliary toxic effects (14.4% vs. 4.8%) and prolonged QT interval (4.5% vs. 2.1%).
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