medwireNews: Women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer derive a significant progression-free survival (PFS) benefit from the addition of ribociclib to letrozole in the first-line setting, shows the placebo-controlled MONALEESA-2 trial.
During a median follow-up of 15.3 months, median PFS was not reached for the patients randomly assigned to receive the selective CDK4/6 inhibitor alongside letrozole, and was 14.7 months for those given placebo plus letrozole. This gave a significant hazard ratio of 0.56, which met the trial’s prespecified criterion for superiority.
After 12 months, 72.8% of ribociclib-treated participants remained progression-free, compared with 60.9% of those in the placebo group, with corresponding rates of 63.0% and 42.2% after 18 months, a significant difference at both timepoints.
The overall response rate was higher in the ribociclib than the placebo arm, both in the overall study cohort and in patients with measurable disease at baseline, at 40.7% versus 27.5% and 52.7% versus 37.1%, respectively.
Lead investigator Gabriel Hortobagyi (University of Texas MD Anderson Cancer Center, Houston, USA) presented these prespecified interim analysis results at the ESMO 2016 Congress, held in Copenhagen, Denmark, with simultaneous publication in The New England Journal of Medicine.
The double-blind, phase III Mammary Oncology Assessment of LEE011’s (Ribociclib’s) Efficacy and Safety (MONALEESA-2) trial allocated 668 postmenopausal women with recurrent or metastatic breast cancer not treated systemically to receive letrozole either with oral ribociclib 600 mg/day on a 3-weeks on, 1-week off schedule or with placebo.
Grade 3 or 4 adverse events were more common in the ribociclib compared with the placebo group (81.2 vs 32.7%), with haematological events, such as neutropenia (59.3 vs 0.9%), leukopenia (21.0 vs 0.6%) and lymphopenia (6.9 vs 0.9%), occurring most frequently.
Other common high-grade events were hypertension (9.9 vs 10.9%) and elevated alanine aminotransferase (9.3 vs 1.2%) and aspartate aminotransferase (5.7 vs 1.2%) levels.
Hortobagyi said that the grade 3 and 4 side effects were generally manageable with dose interruptions and reductions, allowing most of the participating women to continue treatment. Moreover, the rate of adverse event-related discontinuation was low, at 7.5% and 2.1% for the ribociclib and placebo arms, respectively, he commented.
The presenter told the press that ribociclib represents “an important advance” for this patient population, and “when it is approved by the appropriate regulatory agencies, ribociclib will be one of the major choices.”
He added: “The results of this trial represent a compelling proof of principle, and suggest a paradigm shift in metastatic, [HR-positive] breast cancer.”
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