Theme

Oncology Clinical Update

MONALEESA-2: First-Line Ribociclib + Letrozole Extends Median OS to >5 Years

Source
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. DOI: 10.1056/NEJMoa2114663. (MONALEESA-2; NCT01958021)

In postmenopausal patients with HR+/HER2- advanced breast cancer, combination therapy demonstrates unprecedented survival benefits.

Population

N = 668
Postmenopausal women
Dx: HR+/HER2- Advanced BC
Setting: First-line

Protocol

Design: Phase 3, Rand., Dbl-blind
Exp: Ribociclib (600mg) + Letrozole
Ctrl: Placebo + Letrozole

Follow-Up

Median Duration: 80 Months
(6.6 Years)
Longest for this setting
Median Overall Survival (mOS)
63.9 Months
Absolute survival gain of 12.5 months vs. Placebo.
Median Overall Survival Comparison

Survival & Risk

24%
Relative Risk Reduction HR 0.76 (95% CI, 0.63-0.93; P=0.008)
6-Year Landmark Survival Rate

Delay in Chemotherapy

Ribociclib significantly delayed the median time to first subsequent chemotherapy compared to placebo.

11.7 Months additional delay

Recommendation: Preferred Standard-of-Care

Given the unprecedented median overall survival exceeding 5 years and consistent benefit across subgroups, Ribociclib + Letrozole should be considered a preferred regimen for first-line treatment of postmenopausal patients with HR+/HER2- advanced breast cancer.

AbbreviationsQuick
Abbreviations: 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. 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.
  2. Lobbezoo DJA, van Kampen RJW, Voogd AC, et al. Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2-positive subtype is associated with the most favorable outcome. Breast Cancer Res Treat 2013;141:507-14.
  3. O’Leary B, Finn RS, Turner NC. Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol 2016; 13:417-30.
  4. Hosford SR, Miller TW. Clinical potential of novel therapeutic targets in breast cancer: CDK4/6, Src, JAK/STAT, PARP, HDAC, and PI3K/AKT/mTOR pathways. Pharmgenomics Pers Med 2014; 7:203-15.
  5. Thangavel C, Dean JL, Ertel A, et al. Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer 2011;18:333-45.
  6. Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 2006;24:1770-83.
  7. Miller TW, Balko JM, Fox EM, et al. ERα-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. Cancer Discov 2011;1:338-51.
  8. Chen P, Lee NV, Hu W, et al. Spectrum and degree of CDK drug interactions predict clinical performance. Mol Cancer Ther 2016;15:2273-81.