Discussion
death, CFS, breast cancer
BREAST CANCER
This exploratory analysis of MONALEESA-3, with a median follow-up of 70.8 months, reports the longest mOS benefit to date (67.6 months in the ribociclib + fulvestrant arm) for a first-line population (de novo or late relapse) in a phase III clinical trial setting in ABC. First-line ribociclib + fulvestrant demonstrated a nearly 16-month improvement in mOS versus fulvestrant alone, with a 33% relative reduction in the risk of death. Additionally, even though more patients in the placebo versus ribociclib arm (35.0% vs. 16.7%) received a CDK4/6i after discontinuing study treatment, patients in the ribociclib arm still experienced an OS benefit. These extended follow-up results clearly demonstrate the magnitude of survival benefit with ribociclib in the first-line setting, which was not fully revealed in the prior exploratory OS analysis of MONALEESA-3 for this subgroup [Postdiscontinuation observations are particularly helpful in providing additional insights into benefit beyond study treatment. The benefit of first-line ribociclib + fulvestrant was demonstrated after discontinuation of study treatment, with prolongation of median PFS2 by 16.1 months. Furthermore, median CFS was delayed by 20.2 months in patients receiving ribociclib in the first-line setting, with a 43% relative reduction in the risk of chemotherapy, compared with those receiving placebo. These postdiscontinuation results, along with the survival benefit demonstrated in MONALEESA-3, strengthen the efficacy profile and confirm the lasting benefit of first-line ribociclib treatment that extends well beyond study treatment. Recently the results of SONIA, which studied first-line NSAI + CDK4/6i followed by second-line fulvestrant versus first-line NSAI followed by second-line fulvestrant + CDK4/6i, were reported, with no significant difference in PFS2 or OS between the treatment arms [This is the third pivotal trial to demonstrate a significant improvement in OS with ribociclib in a first-line setting, and these data align with those of the MONALEESA-2 (first line in combination with letrozole in postmenopausal patients) trial and MONALEESA-7 (first line in combination with NSAI in pre/perimenopausal patients) trial, which demonstrated a 63.9- and 58.7-month mOS, respectively, in patients treated with ribociclib + ET [OS results with other CDK4/6is in combination with fulvestrant have been reported. However, it is important to understand the relevant differences in the patient populations of these studies to help put the data in context. MONALEESA-3 included a broad-spectrum patient population, in which first line was defined as either no prior treatment for breast cancer (de novo patients with no prior exposure to ET) or relapse > 12 months after (neo)adjuvant ET (late relapse) and second line was defined as one prior ET for ABC or relapse ≤ 12 months after the end of (neo)adjuvant therapy (early relapse) [