Combination Therapy Shows Overall Survival Benefit in Advanced Breast Cancer

The addition of Kisqali (ribociclib) to Faslodex (fulvestrant) improved overall survival compared to placebo plus Faslodex in patients with hormone-receptor-positive, HER2-negative advanced breast cancer, according to data from a second interim analysis published in The New England Journal of Medicine.

Earlier research from the MONALESSA-3 trial showed that combining Kisqali and Faslodex worked well in terms of improving progression-free survival (the time from treatment to disease progression or worsening) compared to Faslodex alone in postmenopausal patients with hormone-receptor-positive, HER2-negative advanced breast cancer. This analysis of the ongoing trial was done to further examine the benefits of adding Kisquali to Faslodex to treat this disease subtype.

From June 2015 through June 2016, a total of 726 patients were enrolled in the trial, with 484 patients in the Kisqali group and 242 patients in the placebo group. At the cutoff date for this analysis, 25% of the Kisqali group and 13.2% of the placebo group were still receiving treatment.

At data cutoff for analysis of overall survival, 34.5% of patients in the Kisqali group had died and 44.6% of patients in the placebo group died. The estimated overall survival at 42 months was 57.8% in patients who received Kisqali and 45.9% in patients who received placebo.

Additional subgroup analyses were completed to assess overall survival as it related to first- and second-line therapy. Of the 365 patients who received trial treatment as first-line therapy, 237 patients (26.6%) within the Kisqali group and 128 patients (36.7%) within the placebo group died. Estimated overall survival at 42 months among those who received first-line therapy was 66.9% in the Kisqali group compared to 56.3% in the placebo group.

Of the 346 patients who received trial treatment as second-line therapy, or who had early relapse, 237 patients (43%) in the Kisqali group and 109 patients (55%) in the placebo group died. Patients within the Kisqali subgroup reached a median overall survival of 40.2 months compared to 32.5 months in the placebo group.

Reported adverse events were consistent with the ones from the primary report, and there were no new safety signals. Patients within the Kisqali group generally had more frequent adverse events, the most common grade 3 or grade 4 adverse events being neutropenia and leukopenia.

“The benefits of ribociclib with respect to overall survival in the MONALEESA program are noteworthy in the context of CDK4/6 inhibitors in advanced breast cancer,” the researchers wrote.

Given the consistent positive results researchers have found, they note that further study is needed in other patient subsets.

“The combinations of ribociclib with fulvestrant in the MONALEESA-3 trial and with endocrine therapy, particularly nonsteroidal aromatase inhibitors, in the MONALEESA-7 trial have shown a consistent and meaningful prolongation of survival over placebo … These data support the further study of ribociclib, including in the treatment of early breast cancer.”