The following article features coverage from the European Society for Medical Oncology (ESMO) Congress 2021. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Adding ribociclib to first-line letrozole improves overall survival (OS) by more than 1 year in postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, advanced breast cancer, according to results of the phase 3 MONALEESA-2 trial.1

The results were presented at the European Society for Medical Oncology (ESMO) Congress 2021 by Gabriel N. Hortobagyi, MD, of The University of Texas MD Anderson Cancer Center in Houston.

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MONALEESA-2 ( Identifier: NCT01958021) is a randomized trial comparing ribociclib plus letrozole with placebo plus letrozole in postmenopausal patients with HR-positive, HER2-negative, advanced breast cancer.

Prior results from the trial showed a significant improvement in progression-free survival with ribociclib.2 At ESMO 2021, Dr Hortobagyi reported the final analysis of OS.

The intention-to-treat population included 668 patients — 334 assigned to ribociclib plus letrozole and 334 assigned to placebo plus letrozole.

At the data cutoff of June 10, 2021, 47 patients were still on treatment — 30 in the ribociclib arm and 17 in the placebo arm. Of the remaining patients, 400 had died — 181 in the ribociclib arm and 219 in the placebo arm.

At a median follow-up of 80 months, ribociclib showed a significant OS benefit. The median OS was 63.9 months with ribociclib and 51.4 months with placebo (hazard ratio [HR], 0.76; 95% CI, 0.63-0.93; P =.004).

“This is the longest median survival reported to date in any advanced breast cancer phase 3 clinical trial,” Dr Hortobagyi said.

He noted that ribociclib improved the median OS by 12.5 months, and a consistent OS benefit was seen across subgroups.

Furthermore, the OS benefit with ribociclib increased over time. Ribociclib increased the OS rate by 5.7% at 4 years, 8.4% at 5 years, and 12.2% at 6 years. The estimated 6-year OS rate was 44.2% for ribociclib and 32% for placebo.

Ribociclib also delayed the time to first chemotherapy by about 1 year. The median time to chemotherapy was 50.6 months in the ribociclib arm and 38.9 months in the placebo arm (HR, 0.74; 95% CI, 0.61-0.91).

Among patients who discontinued study treatment, 87.8% in the ribociclib arm and 90.2% in the placebo arm received a subsequent therapy, with 21.7% and 34.4%, respectively, receiving a subsequent CDK4/6 inhibitor.

Dr Hortobagyi said no new safety signals were observed, and most adverse events occurred in the first 12 months of treatment.

“Based on these results, ribociclib and letrozole should be considered the preferred treatment option for hormone receptor-positive, HER2-negative, advanced breast cancer,” Dr Hortobagyi said.

Disclosures: This research was supported by Novartis Pharmaceuticals Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of ESMO 2021 by visiting the conference page.


  1. Hortobagyi GN, Stemmer SM, Burris, HA, et al. Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor 2 negative (HR-positive/HER2-negative) advanced breast cancer (ABC) treated with endocrine therapy (ET) +/- ribociclib (RIB). Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. LBA17_PR.
  2. Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018;29(7):1541-1547. doi:10.1093/annonc/mdy155