MONALEESA-2 secondary analyses support safety and efficacy for ribociclib/letrozole for breast cancer
Catherine Amey, Senior Medical Writer, Touch Medical Media, Goring-On-Thames, UK

More evidence of the efficacy and safety of the cyclin dependent kinase (CDK) 4/6 inhibitor ribociclib plus letrozole as a first-line treatment for hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer was presented, as two abstracts, during the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.1, 2

The first presentation reported second interim analysis of data a median duration of 26.4 months. Progression free survival rate was 54.7% in the combination arm compared with 35.9% in the placebo arm at 24 months, a benefit that was consistent across all patient subgroups.1

There were not enough events to report on overall survival but data are expected within 3 years. Lead author, Gabriel N Hortobagyi of The University of Texas MD Anderson Cancer Centre noted the importance of identifying the most appropriate patients for this and other CDK4/6 inhibitors. “The search for biomarkers in these targeted therapies is critically important”, he said.

More detailed, longer-term data on adverse events in MONALEESA-2 were provided in the second abstract.2 Neutropenia was the most common all grade and grade 3/4 adverse event in the intervention arm (74% and 59%, respectively). Median time to first event for common all-grade ≥2 neutropenia (based on neutrophil counts) in the ribociclib +letrozole arm was 16 days. Other common grade 3/4 adverse events were leukopenia (21% versus 1%), elevated alanine aminotransferase (9% versus 1%), lymphopenia (7% versus 1%), and elevated aspartate aminotransferase (6% versus 1%).

“The data support the current impression of a drug with a high degree of tolerability” remarked lead author, Wolfgang Janni of Heinrich-Heine-University in Germany.

In the phase III MONALEESA trial, 668 postmenopausal women with HR-positive/HER2-negative, previously untreated advanced breast cancer were randomly assigned to ribociclib plus letrozole (600 mg/day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg/day) or placebo plus letrozole. The first interim analysis, at a median follow-up time of 15.3 months, demonstrated that the duration of PFS was significantly extended in the ribociclib group compared with the placebo group (hazard ratio [HR] 0.56; 95% confidence interval [0.43, 0.72]; p = 3.29 × 10−6 for superiority).3

REFERENCES
1. Hortobagyi G, Stemmer, SM, Burris, HA, et al., Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC), J Clin Oncol, 2017;35:(suppl; abstr 1038).
2. Janni w, Burris, HA, Blackwell, KL, et al., First-line ribociclib plus letrozole for postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC): MONALEESA-2 safety results, J Clin Oncol, 2017;35:(suppl; abstr 1047).
3. Hortobagyi GN, Stemmer SM, Burris HA, et al., Ribociclib as first-line therapy for HR-positive, advanced breast cancer, N Engl J Med, 2016;375:1738-48.