Findings from MONALEESA-7, the first dedicated trial investigating a CDK4/6 inhibitor in pre- and peri-menopausal women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, demonstrated that addition of ribociclib to first-line endocrine therapy with tamoxifen/non-steroidal aromatase inhibitor (NSAI) plus goserelin, significantly prolonged progression-free survival (PFS) and had a manageable safety profile. The study validates the clinical utility of ribociclib with multiple endocrine therapies, including tamoxifen, in premenopausal women with HR-positive, HER2-negative advanced breast cancer. The results are presented in an oral session at 2017 San Antonio Breast Cancer Symposium (5-9 December, San Antonio, TX, USA).
The authors wrote in study background that endocrine therapy with ovarian function suppression is an established first-line treatment for pre- and peri-menopausal women with HR-positive, HER2-negative advanced breast cancer. Addition of ribociclib to first-line endocrine therapy prolonged PFS in a phase III trial of postmenopausal women with HR-positive, HER2-negative advanced breast cancer (MONALEESA-2).
The MONALEESA-7 (NCT02278120) is the first double-blind, randomised, phase III trial evaluating ribociclib plus tamoxifen/NSAI and goserelin specifically in pre- and peri-menopausal patients. In particular, pre- or peri-menopausal women with HR-positive, HER2-negative advanced breast cancer who had received at least one line of chemotherapy and no prior endocrine therapy for advanced disease were randomised (1:1) to ribociclib or placebo in combination with either tamoxifen or an NSAI (letrozole or anastrozole) plus goserelin. The primary endpoint was locally assessed PFS. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), and safety.
In total,672 patients were enrolled. Baseline patient characteristics were balanced between treatment arms. The primary analysis was conducted after 318 events had occurred; median time from randomisation to data cut-off date was 19.2 months.
The study met its primary objective, PFS was significantly improved in ribociclib arm with median PFS 23.8 months versus 13.0 months in placebo arm, hazard ratio 0.553 (95% CI: 0.441–0.694; p = 9.83×10–8). Subgroup analyses demonstrated consistent PFS benefits for ribociclib vs placebo.
The ORR was significantly higher among patients with measurable disease at baseline in the ribociclib arm compared with the placebo arm (51% vs 36%, p = 3.17×10–4) and CBR was 80% in ribociclib versus 67% in placebo arm (p = 3.40×10–4).
The most frequent all-grade adverse events (≥25% of patients; ribociclib versus placebo arm) were neutropenia (76% vs 8%), hot flush (34% vs 34%), nausea (32% vs 20%), leukopenia (31% vs 6%), and arthralgia (30% vs 27%). Of these, neutropenia (61% vs 4%) and leukopenia (14% vs 1%) were the only grade 3/4 events reported in ≥5% of patients (ribociclib versus placebo arm). Febrile neutropenia (ribociclib versus placebo arm) occurred in 2% vs <1% of patients. Grade 3/4 QT prolongation (ribociclib versus placebo arm) was reported in 1% versus <1% of patients. Adverse events leading to permanent discontinuation in ribociclib arm occurred in 4% versus 3% of patients on placebo arm.
MONALEESA-7 is the first clinical trial with statistical power to show that ribociclib has clinical benefit specifically in pre- and peri-menopausal women with HR-positive, HER2-negative advanced breast cancer. It is also the first trial to show that ribociclib can be safely and effectively combined with either tamoxifen or a nonsteroidal aromatase inhibitor together with ovarian suppression by goserelin. Howerer, longer follow-up is needed to determine whether the trial will meet its secondary endpoint of overall survival.
Tripathy D, Sohn J, Imribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 San Antonio Breast Cancer Conference, abstract GS2-05.