medwireNews: The addition of the cyclin-dependent kinase (CDK) 4 and 6 inhibitor ribociclib to either oral tamoxifen or a nonsteroidal aromatase inhibitor (NSAI) improves progression-free survival (PFS) in premenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer, according to findings from the phase III MONALEESA-7 study.
Over a median follow-up of 19.2 months, the 335 women randomly assigned to treatment with ribociclib had a 45% lower risk for disease progression than the 337 assigned to the placebo group. They also gained 11 months in PFS, at a median of 23.8 versus 13.0 months, a difference Yen-Shen Lu (National Taiwan University Hospital, Taipei) and colleagues describe as “statistically significant and clinically meaningful.”
Oral ribociclib was given at a dose of 600 mg/day, 3 weeks on and 1 week off, and participants also received either tamoxifen 20 mg/day or letrozole 2.5 mg/day or anastrozole 1 mg/day, and goserelin (3.6 mg on day 1 of every 28-day cycle). All the women were naive to CDK 4 and 6 inhibitor therapy.
The researchers point out that the longer progression of PFS seen with the addition of ribociclib was evident regardless of whether women received tamoxifen or NSAI endocrine therapy.
Significant improvements in the overall response rate, clinical benefit rate, and health-related quality of life scores were also observed with ribociclib compared with placebo.
The most common grade 3 or 4 adverse event was neutropenia, which was experienced by 61% of patients in the ribociclib group and 4% of those in the placebo group. However, the adverse event profile of ribociclib was generally manageable with dose adjustments, and adverse events were responsible for study discontinuation in only 12 (4%) patients in the ribociclib group and 10 (3%) in the placebo group.
Overall, the researchers say, “the results of this trial support a change in practice to extend endocrine therapy plus ribociclib as a first-line treatment for premenopausal patients with [hormone receptor]-positive, HER2-negative, advanced breast cancer.”
In a comment accompanying the study in The Lancet Oncology, Theodoros Foukakis (Karolinska Institutet and University Hospital, Stockholm, Sweden) wrote that that the results “provide substantial evidence for the use of inhibitors of CDKs 4 and 6 in premenopausal women with advanced breast cancer”, although he noted that questions remain regarding “their exact place in treatment.”
The researchers note that although there is a need to improve outcomes for premenopausal women with advanced breast cancer, this patient group is often not included in randomized trials. They say MONALEESA-7 is the first phase III randomized clinical trial to prospectively assess a CDK 4 and 6 inhibitor plus endocrine therapy specifically in this population.
By Catherine Booth
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