Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial.

Abstract

PURPOSE:

Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer.

METHODS:

668 postmenopausal women with HR+, HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger (< 65 years) patients. Secondary endpoints included response rates and safety.

RESULTS:

Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95% CI 0.394-0.937) and younger patients (hazard ratio: 0.523; 95% CI 0.378-0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms.

CONCLUSIONS:

Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2- advanced breast cancer in the first-line setting.

• Authors: Gabe S Sonke, Lowell L Hart, Mario Campone, Frans Erdkamp, Wolfgang Janni, Sunil Verma, Cristian Villanueva, Erik Jakobsen, Emilio Alba, Erik Wist, Anne M Favret, Thomas Bachelot, Roberto Hegg, Paul Wheatley-Price, Farida Souami, Santosh Sutradhar, Michelle Miller, Caroline Germa, Howard A Burris
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 167 Issue 3 Pg. 659-669 (02 2018) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 29058175 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Aminopyridines
• Biomarkers, Tumor
• Nitriles
• Purines
• Receptors, Estrogen
• Receptors, Progesterone
• Triazoles
• Letrozole
• ERBB2 protein, human
• Receptor, ErbB-2
• ribociclib

Topics

• Aged
• Aged, 80 and over
• Aminopyridines (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Biomarkers, Tumor (genetics)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Disease-Free Survival
• Female
• Humans
• Letrozole
• Middle Aged
• Nitriles (administration & dosage, adverse effects)
• Purines (administration & dosage, adverse effects)
• Receptor, ErbB-2 (genetics)
• Receptors, Estrogen (genetics)
• Receptors, Progesterone (genetics)
• Triazoles (administration & dosage, adverse effects)