1. Invasive disease-free survival was significantly higher in patients receiving adjuvant ribociclib + NSAI when compared to patients receiving NSAI alone.

2.Distant disease-free survival and recurrence-free survival also favoured treatment with adjuvant ribociclib + NSAI, compared to NSAI alone.

Evidence Rating Level: 1 (Excellent)

Study Rundown: In this phase 3, randomized, international, open-label trial, 5101 patients with stage II or III HR-positive, HER2-negative breast cancer were assigned to receive either, a reduced dose ribociclib (400 mg PO OD x 21 days, followed by 7 days off x 3 years) + NSAI or to receive NSAI alone (anastrozole). The primary endpoint was invasive disease-free survival with secondary endpoints being distant disease-free survival, recurrence-free survival, overall survival, safety, quality of life, and pharmacokinetics. Results of this prespecified, interim analysis, suggest that adjuvant ribociclib + NSAI significantly lowered the risk of invasive disease when compared to adjuvant therapy with NSAI alone.  This study, much like the monarchE trial, suggests an additional role for CDK4/6 inhibitors in the adjuvant setting for patients with breast cancer though this study does include . The median duration of follow-up of this interim analysis was only 28 months long; given that breast cancer may recur in women up to 20 years post-treatment, long-term follow-up is needed to further assess the efficacy of adjuvant ribociclib + NSAI.

Click to read the study in NEJM

Relevant Reading: Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a pre planned interim analysis of a randomized, open-label, phase 3 trial

In-Depth [randomized-controlled trial]: This study was funded by Novartis and sought to ascertain whether ribociclib might improve invasive disease-free survival amongst patients with early-stage breast cancer. Researchers randomly assigned 5101 patients with anatomical stage II (IIa required additional high-risk features for inclusion) or III, HR-positive, HER2-negative breast cancer to receive either ribociclib (400 mg PO OD x 21 days followed by 7 days off) + NSAI (Letrozole 2.5 mg PO OD or anastrozole 1 mg PO OD) for 36 months, followed by NSAI alone for 14 months or NSAI alone for 60 months. Men and pre-menopausal women in both treatment groups also received gonadal suppression (Goserelin 3.6 mg subcutaneously Q28 days). At 3 years, ribociclib + NSAI compared to NSAI alone showed improved invasive disease-free survival (90.4% vs. 87.1%, HR, 0.75; 95% CI, 0.62-0.91), distant disease-free survival (90.8% vs. 88.6%, HR, 0.74; 95% CI, 0.60-0.91) and recurrence-free survival (91.7% vs. 88.6%, HR, 0.72; 9%% CI, 0.59-0.88).  Neutropenia was a significant adverse event occurring in 62.1% of patients receiving ribociclib + NSAI, with 43.8% of patients in this group reporting grade 3 neutropenia. Arthralgias and liver injury were also reported as significant adverse events, occurring in both treatment groups.  Findings from this study suggest that ribociclib + NSAI significantly lowers the risk of invasive disease in patients with stage II or III HR-positive, HER2-negative breast cancer.

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