Efficacy, Safety, and Patient-Reported Outcomes of Postmenopausal Women with Advanced Breast Cancer Receiving Ribociclib + Fulvestrant: Results from MONALEESA-3

November 2018 Vol 9, NO 11
Karwyn S. Gustafson, RN, MSN
University of New Mexico Comprehensive Cancer Center
Albuquerque, NM
Francisco J. Esteva, MD, PhD
NYU Langone Medical Center,
New York, NY
Peter Jiang, MD
Providence Regional Cancer Partnership and the Everett Clinic
Everett, WA
J. Thaddeus Beck, MD
Highlands Oncology Group, Fayetteville, AR
Dennis J. Slamon, MD, PhD
UCLA Medical Center, Santa Monica, CA

Background: Ribociclib combined with an aromatase inhibitor has been shown to significantly prolong progression-free survival (PFS) in premenopausal1 and postmenopausal2 women with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) who had not been treated previously for ABC.

Objectives: This review highlights the available efficacy, safety, and patient-reported outcomes of ribociclib plus fulvestrant in patients with ABC who had received ≤1 line of prior endocrine therapy (ET).3,4

Methods: MONALEESA-3 (ClinicalTrials.gov identifier, NCT02422615) is a phase 3, double-blind trial of patients randomized 2:1 to receive daily ribociclib 600 mg (3 weeks on/1 week off) or placebo in combination with fulvestrant 500 mg (administered on the first day of every 28-day cycle and cycle 1, day 15). Patients were stratified by presence of liver/lung metastases and prior ET. The primary end point was mean duration of PFS as assessed by investigators. Secondary end points included safety and time to definitive 10% deterioration from baseline (TTD) and change from baseline in global health status/quality of life (GHS/QoL) scale scores (measured by European Organisation for Research and Treatment of Cancer Quality of Life Core 30 Questionnaire). Pain scores were determined using the Brief Pain Inventory, Short Form.

Results: The study included 726 patients and had a median duration of 20.4 months from randomization to data cutoff. Median PFS for ribociclib (n = 484) vs placebo (n = 242) was 20.5 months (95% CI, 18.5-23.5) vs 12.8 months (95% CI, 10.9-16.3), respectively (hazard ratio [HR] 0.593; 95% CI, 0.480-0.732; P = .00000041). The PFS benefit associated with ribociclib was consistent between ET-naive patients (n = 367; HR 0.577; 95% CI, 0.415-0.802) and ET-exposed patients (n = 345; HR 0.565; 95% CI, 0.428-0.744). Most common adverse events for ribociclib vs placebo were neutropenia (70% vs 2%), nausea (45% vs 28%), and fatigue (31% vs 33%), respectively. For the ribociclib group, grades 3 and 4 neutropenia (47%, 7%),3 increased alanine aminotransferase (7%, 2%), and increased aspartate aminotransferase (5%, 1%) were reported.5 Postbaseline QT interval corrected by Fridericia’s formula >480 msec was also reported in the ribociclib (6%) and placebo (3%) groups. Mean GHS/QoL was maintained or improved from baseline during every cycle of treatment in both groups up to cycle 19 (mean change from baseline, ribociclib, 3.6-4.9; placebo, 1.3-4.3). At the end of treatment, ribociclib did not negatively affect the mean change from baseline GHS/QoL (ribociclib, n = 184, –5.2 points; placebo, n = 113, –5.5 points). Median TTD for GHS/QoL for ribociclib vs placebo, respectively, was not reached (NR) vs 19.4 months (HR 0.80; 95% CI, 0.60-1.05); for worst pain, 25.4 months vs NR (HR 0.81; 95% CI, 0.58-1.13); and for pain severity, 25.4 months vs NR (HR 0.81; 95% CI, 0.60-1.11). Median TTD for pain interference index was NR in both groups.

Conclusions: The addition of ribociclib with fulvestrant significantly prolonged PFS, demonstrated a manageable safety profile, and maintained QoL in postmenopausal patients with HR+/HER2− ABC who had previously received ≤1 line of ET for advanced disease.


References

  1. Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19:904-915.
  2. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375:1738-1748.
  3. Slamon DJ, et al. Slides presented at ASCO 2018; June 1-5, 2018; Chicago, IL.
  4. Fasching PA, et al. Abstract presented at ASCO 2018; June 1-5, 2018; Chicago, IL.
  5. Slamon DJ, et al. Abstract presented at ASCO 2018; June 1-5, 2018; Chicago, IL.
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