In a phase II trial (AMALEE) reported in JAMA Oncology, Cardoso et al found that a first-line ribociclib dose of 400 mg was not noninferior to a dose of 600 mg in patients with newly diagnosed hormone receptor–positive, HER2-negative advanced breast cancer.
Study Details
In the open-label noninferiority trial, 376 patients from sites in 23 countries were randomly assigned between June 2019 and December 2020 to receive ribociclib at 400 mg/d (n = 188) for 3 weeks on/1 week off with a nonsteroidal aromatase inhibitor (AI; letrozole or anastrozole) or ribociclib at 600 mg/d (n = 188) for 3 weeks on/1 week off with a nonsteroidal AI. All premenopausal women also received goserelin. The primary outcome measure was objective response rate, with noninferiority being found if the lower bound of the 90% confidence interval (CI) for the difference between 400 and 600 mg was at least 0.814.
Key Findings
Median follow-up was 53.5 months (range = 36.0–64.0 months).
Objective response rates were 48.9% in the 400-mg group vs 56.1% in the 600-mg group, with a response ratio of 0.87 (90% CI = 0.74–1.03), with noninferiority not being achieved.
Median time to response was longer with ribociclib at 400 vs 600 mg (13.1 vs 9.0 months), whereas median duration of response (26.5 vs 28.8 months) and median progression-free survival (26.9 vs 25.1 months) were similar in the two groups.
The ribociclib 400-mg group had a shorter ΔQTcF interval vs the 600-mg group (12.5 vs 19.7 ms at cycle 1 day 15, 2 hours postdose). Grade 3 or 4 neutropenia occurred in 41.0% vs 58.5% of patients. Dose reductions due to adverse events occurred in 15.4% vs 36.9% of patients. Liver and kidney toxicities, interstitial lung disease/pneumonitis, and treatment discontinuations due to adverse events were similar in the two groups.
The investigators concluded: “The AMALEE randomized clinical trial did not demonstrate [objective response rate] noninferiority of ribociclib, 400 mg vs ribociclib, 600 mg, with comparable [duration of response and progression-free survival] between doses. Ribociclib, 400 mg had longer [time to response], lower pharmacokinetic exposure, and lower rates of QTcF prolongation and neutropenia. The final results confirmed the standard ribociclib, 600 mg starting dose in [hormone receptor–positive, HER2-negative advanced breast cancer] while supporting dose reduction to manage dose-dependent [adverse events].”
Fatima Cardoso, MD, of Medical Oncology, ABC Global Alliance, Lisbon, Portugal, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Novartis Pharmaceuticals Corporation. For full disclosures of all study authors, visit jamanetwork.com.
