2O - Analysis of Asian and non-Asian patients (pts) from the NATALEE trial of ribociclib (RIB) + a nonsteroidal aromatase inhibitor (NSAI) in pts with HR+/HER2− early breast cancer (EBC)

Background

NATALEE showed statistically significant invasive disease–free survival (iDFS) benefit with RIB + NSAI vs NSAI in a broad pt population with stage II/III HR+/HER2− EBC at risk of recurrence (HR 0.72, 44.2 mo median follow-up). We report efficacy, quality-of-life (QOL), and safety data from an exploratory analysis of Asian and non-Asian pts in NATALEE (data cutoff; April 29, 2024).

Methods

Pts were randomized 1:1 to RIB (400 mg/d; 36 mo) + NSAI vs NSAI. NATALEE included pts with stage II/III disease (AJCC 8th ed) with additional high-risk criteria for stage IIA N0 grade 2 disease. Pts with Asian/non-Asian race were analyzed regardless of geographic location. As this is an exploratory analysis, data should be interpreted with caution.

Results

Asian (n = 675) and non-Asian (n = 4161) pts, respectively, differed in age (median, 48.0 vs 53.0 y), BMI (median, 23.2 vs 27.0 kg/m2), premenopausal status (60.9% vs 41.1%), stage II (25.2% vs 42.5%) and III (74.8% vs 57.1%) disease, and prior chemotherapy (96.1% vs 86.3%). However, pt characteristics were balanced between RIB + NSAI and NSAI arms within Asian and non-Asian groups. iDFS benefit with RIB + NSAI vs NSAI was noted in Asian (HR 0.63 [95% CI: 0.40-1.01]) and non-Asian pts (HR 0.73 [95% CI: 0.61-0.87]). Distant disease–free survival benefit with RIB + NSAI vs NSAI was also seen in Asian (HR 0.67 [95% CI: 0.41-1.08]) and non-Asian pts (HR 0.73 [95% CI: 0.60-0.87]). Median time to deterioration (>10% decrease) in EORTC QLQ-C30 physical functioning (Asian: HR 1.00; non-Asian: HR 0.98) and global health status (Asian: HR 1.04; non-Asian: HR 1.04) was similar with RIB + NSAI vs NSAI. While there were no new safety signals, Asian pts on RIB + NSAI had higher rates of dose reductions (33.8% vs 21.0%) and interruptions (83.5% vs 64.4%) due to adverse events (AEs) but lower rates of RIB discontinuations due to AEs (14.4% vs 21.2%) and RIB discontinuations due to AEs without prior RIB dose reductions (7.9% vs 15.4%) than non-Asian pts.

Conclusions

This exploratory analysis of NATALEE shows Asian pts treated with RIB + NSAI derive clinically meaningful efficacy benefit with manageable safety and QOL maintenance.

Clinical trial identification

NCT03701334.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Safiyya Ali, MSc, CMPP and Shashank Tandon, PhD of Nucleus Global.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

B. Xu: Financial Interests, Personal, Advisory Role, Advisory Fees: Novartis, AstraZeneca. J. Sohn: Financial Interests, Institutional, Research Grant, Research grant / Funding (institution): MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, and Boehringer Ingelheim. Y.H. Park: Financial Interests, Personal, Advisory Board: MSD, Pfizer, Roche, Novartis, AstraZeneca, Daiichi Sankyo, Helsinn; Financial Interests, Personal, Invited Speaker: MSD, Pfizer, Roche, Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: MSD, Pfizer, Roche, AstraZeneca, Gencurix, GenomeInsight; Other, Personal, Principal Investigator: MSD, Pfizer, Roche, Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Other: Gilead. C. Huang: Financial Interests, Institutional, Invited Speaker, Speakers bureaus: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, speakers bureaus: AstraZeneca, Pfizer, Novartis, Roche, Eli Lilly, Gilead; Financial Interests, Institutional, Research Grant, research grants to institution: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Research grants to institution: AstraZeneca, EirGenix, Eli Lilly, MSD, OBI Pharma, Pfizer, Roche, Novartis, Seagen, Gilead, Aston Sci; Non-Financial Interests, Personal, Advisory Role, Advisory boards: Daiichi Sankyo, AstraZeneca, Eli Lilly, Pfizer, Novartis, Roche. Y. Lu: Other, Personal and Institutional, Other, Clinical Trial Study Fee: Novartis; Financial Interests, Personal and Institutional, Research Grant, Grant for clinical study for ESR1 mutation detected by cell free DNA: Novartis; Financial Interests, Personal, Advisory Board: Novartis, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis, Eisai, Eli Lilly, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer; Financial Interests, Personal, Invited Speaker, Contracted research, speaker: Roche, Merck Sharp & Dohme, Pfizer, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Merck Sharp & Dohme, Pfizer, AstraZeneca. K.H. Jung: Financial Interests, Personal, Advisory Board: MSD, Daiichi Sankyo, Pfizer, Eisai, AstraZeneca, Roche, Gilead Science, Novartis. A. Chan: Financial Interests, Personal and Institutional, Research Funding: Eisai. D. Slamon: Financial Interests, Personal, Member of Board of Directors, Board of Directors (Stock): Biomarin; Non-Financial Interests, Personal, Other, Travel expenses: Biomarin, Pfizer, Novartis; Financial Interests, Personal, Stocks or ownership: Pfizer, Amgen, Seattle Genetics, 1200 Pharma, TORL BioTherapeutics; Financial Interests, Institutional, Research Funding: Pfizer, Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting: Novartis, Eli Lilly; Financial Interests, Personal and Institutional, Other, Founder: 1200 Pharma, TORL BioTherapeutics; Financial Interests, Personal, Advisory Board: Novartis. V. Sakalosh: Financial Interests, Personal and Institutional, Other, Translational Research In Oncology is contracted by Novartis as CRO conducting the NATALEE trial: Novartis. M. Gao, S. Islam: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Local PI, Clinical Trial Budget: AstraZeneca, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Coordinating PI, Clinical Trial Budget: Eisai; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. All other authors have declared no conflicts of interest.