TOPLINE:

Ribociclib 400 mg did not demonstrate noninferiority to the 600-mg dose in patients with hormone receptor-positive (HR+) advanced breast cancer, but it was associated with better tolerability with lower rates of adverse events (AEs).

METHODOLOGY:

• The current standard of care for HR+/ERBB2- advanced breast cancer involves endocrine therapy plus a cyclin-dependent kinase 4/6 inhibitor. Previous phase 3 MONALEESA trials demonstrated substantial survival benefits with ribociclib 600 mg, though dose-dependent AEs were noted.
• A phase 2, multicenter, randomized, open-label, noninferiority study enrolled 376 pre- and postmenopausal women with newly diagnosed HR+/ERBB2- advanced breast cancer.
• Research was conducted across 107 sites in 23 countries spanning Europe, Australia, Latin America, North America, and Asia, with data analyzed at final cutoff on August 30, 2024.
• Participants were randomly assigned 1:1 to receive ribociclib 400 mg or 600 mg plus a nonsteroidal aromatase inhibitor (NSAI), with premenopausal patients also receiving goserelin.
• Primary endpoint was overall response rate, and secondary endpoints were Q-T interval changes, duration of response, time to response, progression-free survival, pharmacokinetics, and safety.

TAKEAWAY:

• Overall response rate (ORR) was 48.9% with ribociclib 400 mg compared with 56.1% with ribociclib 600 mg (ratio, 0.87; 90% CI, 0.74-0.83), failing to meet noninferiority criteria.
• AEs occurred in 95.7% of patients receiving ribociclib 400 mg and in 96.8% receiving ribociclib 600 mg, with grade 3 or higher events affecting 65.4% and 79.3% of patients, respectively.
• In those receiving ribociclib 400 mg vs 600 mg, the most common grade 3 or higher AEs were neutropenia (41.0% vs 58.5%) and increased alanine aminotransferase levels (14.4% vs 11.7%).

IN PRACTICE:

“The results of the AMALEE randomized clinical trial, specifically the greater ORR and shorter [time to response] with ribociclib 600 mg plus NSAI vs ribociclib 400 mg plus NSAI, support continued use of 600 mg as the initial dose of ribociclib in first-line treatment for patients with [HR+/ERBB2- advanced breast cancer]. The findings also support dose reduction to 400 mg as an effective option to manage AEs,” the authors of the study wrote.

SOURCE:

The study was led by Fatima Cardoso, MD, Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation and ABC Global Alliance in Lisbon, Portugal. It was published online on September 25 in JAMA Oncology.

LIMITATIONS:

According to the authors, the AMALEE trial was not designed to assess overall survival or patient-reported outcomes, which were secondary endpoints in the MONALEESA trials. The study was also not designed to compare ribociclib 400 mg plus NSAI with NSAI alone. The COVID pandemic led to protocol deviations affecting efficacy assessments and treatment compliance, though these were balanced between arms. Additionally, the trial was only powered to assess overall response rate as requested by the FDA, not progression-free survival as in a phase 3 study, limiting statistical comparisons between dose levels.

DISCLOSURES:

This study was supported by Novartis Pharmaceuticals Corporation, which was responsible for study design, conduct, data collection, analysis, interpretation, manuscript preparation, and submission. Cardoso disclosed receiving personal fees from Novartis, Pfizer, and other pharmaceutical companies. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.