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MONALEESA-2 Phase 3 Results

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Source: Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022;386:942-50. This document reports the final overall survival analysis of the MONALEESA-2 trial.

First-Line Ribociclib + Letrozole in HR+/HER2- Advanced Breast Cancer
Hortobagyi et al., NEJM (2022) • Median Follow-up: 6.6 Years

Median OS Gain
+12.5 Months

Ribociclib arm: 63.9 mo vs. 51.4 mo (Placebo).

Relative Risk Reduction
24%
HR: 0.76 (95% CI, 0.63–0.93; P=0.008)
N=668 Patients
Postmenopausal, HR+/HER2-
Intervention
Ribociclib (600mg) + Letrozole
Longest Follow-up
Median 80 Months (6.6 Yrs)

Median Overall Survival

First time median OS > 5 years reported in this setting.

6-Year Survival Rate

Group Survival %
Ribociclib + Let. 44.2%
Placebo + Let. 32.0%

Safety Profile

No new safety signals observed despite longer treatment exposure (20.2 vs 14.1 months).

Clinical Recommendation

Adopt Ribociclib plus Letrozole as a preferred first-line standard of care. The data demonstrates a statistically significant OS benefit of >1 year, validating this combination to maximize longevity before disease progression.

AbbreviationsQuick
CDK4/6, cyclin-dependent kinases 4 and 6; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; NE, could not be estimated; PgR, progesterone receptor.
Bibliography8
  1. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022;386:942-50. (DOI: 10.1056/NEJMoa2114663)
  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;375:1738-48.
  3. Im S-A, Lu Y-S, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med 2019; 381: 307-16.
  4. Slamon DJ, Neven P, Chia S, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med 2020; 382: 514-24.
  5. Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med 2018; 379:1926-36.
  6. Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 2017;35:3638-46.
  7. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2016; 17:425-39.
  8. Başaran GA, Twelves C, Diéras V, Cortés J, Awada A. Ongoing unmet needs in treating estrogen receptor-positive/HER2-negative metastatic breast cancer. Cancer Treat Rev 2018; 63:144-55.
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