LBA13 - Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (Pts) with HR+/HER2− early breast cancer (EBC): 4-year outcomes from the NATALEE trial

Background

The phase 3 NATALEE trial demonstrated that adding RIB to adjuvant NSAI led to a statistically significant invasive disease-free survival (iDFS) benefit in pts with stage II and III HR+/HER2− EBC. We present efficacy and safety data of an exploratory analysis with all pts now off RIB.

Methods

Pts were randomized 1:1 to RIB (400 mg/d; 3 wk on/1 wk off for 3 y) + NSAI (letrozole 2.5 mg/d or anastrozole 1 mg/d, for 5 y) or NSAI alone. Men and premenopausal women received goserelin. Eligible pts had BC anatomic stage IIA (either N0 with additional risk factors or N1 [1-3 axillary lymph nodes]), IIB, or III per AJCC (8th ed). The primary endpoint of iDFS and secondary efficacy endpoints distant disease-free survival (DDFS) and overall survival (OS) are reported in this descriptive analysis. Survival was evaluated by Kaplan-Meier method and statistical comparison made by stratified log-rank test.

Results

At data cutoff (29 Apr 2024), all pts in the RIB+NSAI arm (n=2549) were off RIB treatment: 1601 (62.8%) completed 3 y of RIB; 509 (20.0%) stopped RIB early due to adverse events. Median iDFS follow-up was 44.2 mo. RIB+NSAI demonstrated a significant iDFS benefit over NSAI alone (HR, 0.715; 95% CI, 0.609-0.840; P<.0001), with iDFS rates of 90.8% vs 88.1% at 3 y and 88.5% vs 83.6% at 4 y (absolute improvement of 2.7% and 4.9%, respectively). This iDFS benefit was observed across subgroups, including nodal status (absolute 4-y benefit: N0, 5.1%; N+, 5.0%) and stage (absolute 4-y benefit: stage II, 4.3%; stage III, 5.9%). RIB + NSAI vs NSAI alone had a DDFS benefit (HR, 0.715; 95% CI, 0.604-0.847). OS remains immature but trended to favoring RIB (HR, 0.827; 95% CI, 0.636-1.074). Safety remained consistent with prior analyses.

Conclusions

In this 4-y landmark analysis, RIB + NSAI reduced the risk of invasive and distant disease recurrence by 28.5% compared with NSAI. This benefit was maintained after the planned 3-y RIB treatment duration, resulting in an increasing absolute benefit up to 4 y. These results further support the addition of RIB to adjuvant NSAI in a broad population of pts with HR+/HER2− EBC at risk of recurrence.

Clinical trial identification

NCT03701334.

Editorial acknowledgement

Editorial assistance in the writing of this abstract was provided by Casey Nielsen, PhD of Nucleus Global.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Sanofi Aventis, Medac, Menarini, Veracyte; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen, Gilead, Mylan; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Local PI: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v.. D. Yardley: Financial Interests, Institutional, Research Funding, Research funding to institution: Ambrx, Amgen, AstraZeneca, BIOMARIN, Biothera Pharmaceuticals, Clovis Pharma, Dana Farber Cancer Institute, Lilly, Roche/Genentech, G1 Therapeutics, Gilead, Incyte, Innocrin, MacroGenics, MedImmune, Medivation, Merck, Merrimack Pharmaceuticals, Nektar, No; Financial Interests, Institutional, Advisory Role, Payment to institution: AstraZeneca, G1 Therapeutics, Gilead, Immunomedics, Integra, Novartis, Sanofi-Aventis, Stemline,. 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, Advisory Role, Advisory boards: Daiichi Sankyo, AstraZeneca, Eli Lilly, Pfizer, Novartis, Roche. J.P. Crown: Financial Interests, Personal, Other, Travel support to meetings: Novartis, MSD Oncology, Pfizer, Roche, AstraZeneca, Regeneron; Financial Interests, Personal, Other: Pierre Fabre, Novartis, AstraZeneca, Regeneron, Immunocore; Financial Interests, Personal, Stocks/Shares: Oncoassure, Akkure. A. Bardia: Financial Interests, Institutional, Research Grant, Paid to institution: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Mersana, Innocrin, Biothernostcis, Inc.; Financial Interests, Personal, Advisory Board: Biothernostics, Inc.; Financial Interests, Personal, Advisory Board, Advisory Board/Consulting; Steering Committee. Travel support: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics; Financial Interests, Personal, Advisory Board, Advisory Board/Consulting. Travel support: Spectrum Pharma, Taiho, Sanofi; Financial Interests, Personal, Advisory Board, Advisory Board: Daiichi Pharma, PUMA. S. Chia: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Hoffman LaRoche, Eli Lilly, Merck, AstraZeneca; Financial Interests, Institutional, Research Grant, My institution received funds for participation in clinical trials: Novartis, Pfizer, Hoffman LaRoche, Eli Lilly, Merck, AstraZeneca. 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. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarinio-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, Puma; Non-Financial Interests, Member of Board of Directors: TRIO; Non-Financial Interests, Leadership Role: GEICAM; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Board: SEOM. B. Xu: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche, and Eisai. S. Loi: Financial Interests, Institutional, Advisory Board, Consultant: AstraZeneca, Novartis, Roche Genentech; Financial Interests, Institutional, Advisory Board, COnsultant: BMS; Financial Interests, Institutional, Advisory Board, consultant: Daiichi Sankyo, Eli Lilly, Gilead Sciences, Merck; Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, BMS, Amaroq Therapeutics, Mersana Therapeutics, Domain Therapeutics; Financial Interests, Institutional, Funding, Research: Novartis, BMS, Merck, PUMA Biotechnology, Eli Lilly, Nektar Therapeutics, AstraZeneca, Seattle Genetics, Roche - Genentech; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Roche Genentech; Non-Financial Interests, Advisory Role, consultant (not compensated): Eli Lilly, Gilead Therapeutics. C.H.E. Barrios: Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Novartis, Pfizer, Roche, MSD, AstraZeneca, Lilly; Financial Interests, Personal, Advisory Board, Scientific Presentations Consulting AD Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Consulting Scientific presentations: GILEAD; Financial Interests, Personal, Ownership Interest, Virtual APP: THUMMI; Financial Interests, Personal, Stocks/Shares, Clinical Research Company: MEDSIR; Financial Interests, Personal, Ownership Interest, Clinical Research Company: Centro de Pesquisa em Oncologia - CPO; Financial Interests, Institutional, Research Grant, Research Funding To The Institution: Pfizer, Amgem, Gsk, Lilly, Sanofi, Merk, Biomarin, BMS, Medivation, Exelixis, Merck Kgaa, Shangai Henlius Biothech, Polyphor, Pharmamar; Financial Interests, Institutional, Research Grant, Research Funding To The Institution Steering Committee: Novartis, AstraZeneca, Daiichi; Financial Interests, Institutional, Research Grant, Research Funding to the Institution Steering committee: ROCHE; Financial Interests, Institutional, Local PI, Research funding to the institution: Nektar, Regeneron, Janssen, OBI Pharma, Seagen, Checkpoint Therapeutics, Novocure, Aveo Oncology, Takeda, Celgene, TRIO, PPD, Syneos health, DOCS, Labcorp, IQIVIA, Parexel, Nuvisan, PSI, Medplace; Financial Interests, Institutional, Local PI, Research funding to the institutionSteering committee: Myovant; Non-Financial Interests, Member of Board of Directors, Member of Executive Board up to March 2023: BIG International Group; Non-Financial Interests, Leadership Role, Latin American Cooperative Oncology Group: LACOG; Non-Financial Interests, Other, Chair, International Educational Steering Group: ASCO; Non-Financial Interests, Advisory Role, Member Compliance Committee: ESMO. M. Untch: Financial Interests, Institutional, Invited Speaker, All fees and honoraria to the employer/institution: AstraZeneca, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Seagen, Pierre Fabre, Sanofi Aventis, Myriad, Gilead, Novartis, Stemline, Genzyme, Medac. R. Moroose: Financial Interests, Personal, Speaker’s Bureau: Gilead, Lilly, Pfizer, Seattle Genentics, Genentech; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting: J&J. G.N. Hortobagyi: Financial Interests, Institutional, Research Grant, Grant support to my institution to conduct trial: Novartis; Financial Interests, Personal, Steering Committee Member, Personal fees as member and chair of the Steering Committee: Novartis. D. Slamon: Financial Interests, Personal, Member of Board of Directors: Biomarin; Financial Interests, Personal, Stocks/Shares: Biomarin, Pfizer, Amgen, Seattle Genetics, 1200 Pharma, TORL BioTherapeutics; Financial Interests, Personal and Institutional, Research Funding: Pfizer, Novartis; Financial Interests, Personal, Other, Travel expenses: Pfizer, Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting: Novartis, Eli Lilly; Financial Interests, Personal and Institutional, Other, Founder: 1200 Pharma, TORL BioTherapeutics. S. Waters: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks or ownership: Novartis. S.A. Hurvitz: Financial Interests, Personal, Invited Speaker: Clinical Care Options, axis medical, cancer expert now, ICHE, MJH Associates, PER, Primo, Projects in Knowledge, Prova Education, Research to Practice, Ultimate Medical Academy, Vaniam, WebMD, Peer Education, PrecisCA, Peer Voice, Curio, Reach MD/MedIQ, Imedex, MD Outlook, Prime Oncology, Reach MD, OncLive; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Personal, Royalties, author medical book: McGraw; Financial Interests, Personal, Royalties: Elsevier, Springer, Sage, Wolters Kluwer, Wiley; Financial Interests, Institutional, Local PI: Ambrx, AstraZeneca, Arvinas, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Pieris, PUMA, Radius, sanofi, Seattle Genetics, Dignitana, Zymeworks, Phoenix Molecular Designs, Ltd, cytomx, Dantari, G1 Therapeutics, Greenwich Life Sciences, Loxo Oncology, orinove, Orum; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, Celcuity; Financial Interests, Institutional, Research Grant: Ambrx; Financial Interests, Steering Committee Member: Greenwich Life Sciences, Orum; Non-Financial Interests, Advisory Role: Daiichi Sankyo, Novartis, Ambrx, 4DPharma, Dantari, Macrogenics, Lilly, Artios, Roche, Pyxis, Amgen, Pieris, Arvinas, Immunomedics/Gilead, Briacell, Jazz Pharmaceuticals, Boehringer Ingelheim, Stemline/Menarini; Non-Financial Interests, Principal Investigator: Daiichi Sankyo, Genentech, Seattle Genetics; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Other, speaker: National Breast Cancer Coalition; Non-Financial Interests, Member, site representative for breast cancer guidelines: National Comprehensive Cancer Network. All other authors have declared no conflicts of interest.