LBA23 - Invasive disease–free survival (iDFS) across key subgroups from the phase III NATALEE study of ribociclib (RIB) + a nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2- early breast cancer (EBC)

Background

The NATALEE trial demonstrated a statistically significant iDFS benefit with RIB + NSAI vs NSAI alone in a broad population of pts with stage II or III HR+/HER2− EBC at risk of recurrence (Slamon D, et al. ASCO 2023. Oral LBA500). Evaluating iDFS outcomes in clinically relevant subgroups is important for understanding treatment (tx) benefit in specific pts. Here we present a prespecified exploratory subgroup analysis of iDFS in pts enrolled in NATALEE.

Methods

Pts with HR+/HER2− EBC were randomized 1:1 to RIB for 3 y (400 mg/d for 3 wk on/1 wk off) + NSAI for ≥5 y (letrozole 2.5 mg/d or anastrozole 1 mg/d) or NSAI alone. Premenopausal women and men received goserelin every 28 d. NATALEE included pts with anatomical stage IIA (N0 requiring additional risk factors or N1 [1-3 axillary lymph nodes]) and all pts with stage IIB or III disease per AJCC’s Cancer Staging Manual (8th ed). iDFS was evaluated by Kaplan-Meier methods. iDFS analysis was performed according to anatomical stage, menopausal status, nodal status, age, and Ki-67 score (locally tested). This prespecified analysis was not powered for statistical significance.

Results

A total of 5101 pts were included in this analysis (data cutoff: 11 Jan 2023; median follow-up for iDFS, 27.7 mo in both arms). Overall, the iDFS benefit with RIB + NSAI vs NSAI alone was consistent across all clinically relevant subgroups (Table), which in turn was consistent with that observed in the overall trial population.

Conclusions

The iDFS benefit with RIB + NSAI was generally consistent with that in the intent-to-treat population of NATALEE and was not driven by any particular subgroup. The results further support RIB + NSAI as a new tx of choice in a broad population of pts with HR+/HER2− EBC. Table: LBA23

Clinical trial identification

NCT03701334.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Casey Nielsen of MediTechMedia.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

A. Bardia: Financial Interests, Institutional, Research Grant: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Mersana, Innocrin; Financial Interests, Personal and Institutional, Advisory Board: Biothernostics Inc.; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Biothernostics Inc.; Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Spectrum Pharma, Taiho, Sanofi, Daiichi Pharma, Puma; Financial Interests, Personal, Steering Committee Member: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Spectrum Pharma, Taiho, Sanofi, Daiichi Pharma, Puma; Financial Interests, Personal, Other, Travel support: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Spectrum Pharma, Taiho, Sanofi. G.N. Hortobagyi: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Steering Committee Member: Novartis. N.P. McAndrew: Financial Interests, Institutional, Funding: Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Daiichi Sankyo, AstraZeneca, GoodRx; Financial Interests, Personal, Advisory Board: Novartis, Daiichi Sankyo, Biotheranostics, Genomic Health; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Institutional, Funding, Contracted research funding paid to my institution: Daiichi Sanyko, Seattle Genetics, Dizal; Financial Interests, Personal, Other, Travel accommodation: TRIO, Daiichi Sankyo, Roche. J. Sohn: Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim; Financial Interests, Institutional, Funding: MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim; Other, Personal, Stocks/Shares, Stock/Immediate family member: Daiichi Sankyo. L. Hart: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis. S. Im: Financial Interests, Institutional, Research Grant: AstraZeneca, Daewoong Pharm; Financial Interests, Personal, Advisory Board: AstraZeneca, Hanmi, Pfizer; Financial Interests, Institutional, Advisory Board: Novartis; Non-Financial Interests, Personal, Other, Travel support: Novartis; Financial Interests, Personal, Advisory Role: Eisai, Amgen, Roche, Lilly, GSK, MSD. N. Harbeck: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Roche, Sandoz/Hexal, Gilead, Seagen; Financial Interests, Personal, Other, Lectures: Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, MSD, Pierre-Fabre, Roche, Gilead, Seagen; Non-Financial Interests, Personal, Leadership Role, Co-Director WSG: West German Study Group. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie, Agendia, Amgen, Aptitude, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunome, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Odonate Therapeutics, Pfizer, Puma, Prime, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre, Samsung, Sanofi. B. Xu: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Lectures: AstraZeneca, Pfizer, Roche, Eisai. C.H. Barrios: Financial Interests, Institutional, Research Grant: Pfizer, Pharma Mar, Polyphor, Henlius Biotech, Shanghai, Merck KGaA, Millennium, LEO Pharma, ImClone Systems, Exelixis, Medivation, Asana Biosciences, AB Science, Abraxis Biosciences, Daiichi Sankyo, Bristol Myers Squibb, BioMarin, Astellas Pharma, AbbVie, Merck (MSD), Merrimack, Mylan, Taiho Pharmaceutical, Sanofi, GSK, Roche/Genentech, Lilly, Boehringer Ingelheim, Novartis, AstraZeneca, Amgen, Pfizer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Sanofi, Lilly, Zodiac, AstraZeneca, MSD, Bayer, Eisai, Roche/Genentech, Pfizer, Novartis, GSK, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor: Boehringer Ingelheim, Sanofi, Lilly, Zodiac, AstraZeneca, MSD, Bayer, Eisai, Roche/Genentech, Pfizer, Novartis, GSK, Daiichi Sankyo; Financial Interests, Personal, Stocks or ownership: MedSIR, Thummi. R. Moroose: Financial Interests, Personal, Speaker’s Bureau: Gilead, Lilly, Pfizer, Seattle Genentics, Genentech; Financial Interests, Personal, Speaker, Consultant, Advisor: J&J. V. Gonzalez: Other, Institutional, Other, Translational Research In Oncology is contracted by Novartis as CRO conducting the NATALEE trial.: Novartis. R. Fresco: Other, Institutional, Other, TRIO is contracted by Novartis as CRO conducting the NATALEE trial: Novartis. F. Ghaznawi: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks or ownership: Novartis. S. Waters: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. A. Chakravartty: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. D. Slamon: Financial Interests, Personal, Member of Board of Directors: Biomarin; Financial Interests, Personal, Stocks or ownership: Biomarin, Pfizer, Amgen, Seattle Genetics, 1200 Pharma, TORL BioTherapeutics; Financial Interests, Personal, Other, Travel expenses: Biomarin, Pfizer, Novartis; Financial Interests, Institutional, Research Funding: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Novartis; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor: Eli Lilly; Financial Interests, Personal, Leadership Role, Founder: 1200 Pharma, TORL BioTherapeutics. All other authors have declared no conflicts of interest.