LBA17_PR - Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB)

Background

ML-2 (NCT01958021) is a randomized phase III clinical trial investigating first-line (1L) RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), + letrozole (LET) vs placebo (PBO) + LET in postmenopausal pts with HR+/HER2− ABC. ML-2 previously reported a statistically significant improvement in progression-free survival (PFS; primary endpoint) with RIB + LET vs PBO + LET (HR, 0.56; 95% CI, 0.43-0.72). We report the protocol-specified final analysis of OS (key secondary endpoint).

Methods

Postmenopausal pts with HR+/HER2− ABC were randomized 1:1 to receive RIB + LET or PBO + LET. Pts were excluded if they received a prior CDK4/6i, chemotherapy (CT), or ET in the advanced setting. OS was evaluated with a stratified log-rank test and summarized using Kaplan–Meier methods. This protocol-specified analysis was planned after 400 deaths.

Results

The intention-to-treat population included 668 pts (RIB: 334; PBO: 334). At data cutoff (10 June 2021), 47 pts were still on treatment (RIB: 30 [9.0%]; PBO: 17 [5.1%]) and the median follow-up was 79.7 mo (min, 74.6 mo). Final OS was evaluated after 400 deaths (RIB: 181 [54.2%]; PBO: 219 [65.6%]). RIB + LET showed a significant OS benefit vs PBO + LET (median, 63.9 vs 51.4 mo; HR, 0.76; 95% CI, 0.63-0.93; P=.004) and met the boundary of statistical significance. Estimated 6-year OS rate was 44.2% for RIB vs 32.0% for PBO. Time to first CT (median, 50.6 vs 38.9 mo; HR, 0.74; 95% CI, 0.61-0.91) and CT-free survival (median, 39.9 vs 30.1 mo; HR, 0.74; 95% CI, 0.62-0.89) showed a consistent benefit for RIB vs PBO. Among pts who discontinued study treatment, 87.8% vs 90.2% received a subsequent antineoplastic therapy for RIB vs PBO, respectively, and 21.7% and 34.4% received a subsequent CDK4/6i. No new safety signals were observed.

Conclusions

To date, this is the first report of a statistically significant and clinically meaningful OS benefit with a 1L CDK4/6i in postmenopausal pts with HR+/HER2– ABC. After a median follow-up of >6.5 y, median OS improvement was >12 mo for 1L RIB + LET vs PBO + LET.

Clinical trial identification

NCT01958021 (CLEE011A2301).

Editorial acknowledgement

This abstract was developed with editorial assistance provided by Casey Nielsen, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

G.N. Hortobagyi: Financial Interests, Personal, Research Grant, Grant support to institution to conduct trial. Personal fees member/chair Steering Committee: Novartis. S.M. Stemmer: Financial Interests, Institutional, Research Grant: Rabin Medical Center. H.A. Burris III: Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Novartis; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: AstraZeneca; Financial Interests, Institutional, Other, Payment to institution for consulting services performed by Dr. Burris: AstraZeneca; Financial Interests, Institutional, Other, Payment to institution for consulting services performed by Dr. Burris: FORMA Therapeutics; Financial Interests, Institutional, Other, Payment to institution for consulting services performed by Dr. Burris: Celgene; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Incyte; Financial Interests, Institutional, Other, ayment to institution for consulting services performed by Dr. Burris: Incyte; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Roche; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: MedImmune; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Macrogenics; Financial Interests, Institutional, Other, Payment to institution for expert testimony performed by Dr. Burris: Novartis; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Lilly; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Seattle Genetics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Merck; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Aglos; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Jounce Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Moderna Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: CytomX Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: GlaxoSmithKline; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Verastem; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Tesaro; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: BioMed Valley Discoveries; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: TG Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Vertex; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: eFFECTOR Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Janssen; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Gilead Sciences; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: BioAtla; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: CicloMed; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Harpoon Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Arch; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Arvinas; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Revolution Medicines; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Array BioPharma; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Bayer; Non-Financial Interests, Personal, Other, Non-compensated consulting services performed by Dr. Burris: Bayer, Pfizer, Novartis; Financial Interests, Institutional, Invited Speaker, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: BIND Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Kyocera; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: miRNA Therapeutics; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Pfizer; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Takeda/Millennium; Financial Interests, Institutional, Principal Investigator, Payment to institution for conduct of clinical trial in which Dr. Burris served as PI.: Foundation Medicine; Non-Financial Interests, Personal, Other, Uncompensated consulting work: Daiichi Sankyo; Financial Interests, Personal and Institutional, Full or part-time Employment: HCA Healthcare/Sarah Cannon; Financial Interests, Personal and Institutional, Leadership Role: HCA Healthcare/Sarah Cannon; Financial Interests, Personal and Institutional, Stocks/Shares: HCA Healthcare/Sarah Cannon; Non-Financial Interests, Personal, Other, Non-compensated consulting services performed by Dr. Burris: GRAIL. Y.S. Yap: Financial Interests, Personal, Other, not specified: Novartis; Non-Financial Interests, Personal, Other, not specified: Novartis; Financial Interests, Personal, Other, not specified: Pfizer; Non-Financial Interests, Personal, Other, not specified: Pfizer; Financial Interests, Personal, Other, not specified: Lilly; Non-Financial Interests, Personal, Other, not specified: Lilly; Financial Interests, Personal, Other, not specified: AstraZeneca; Non-Financial Interests, Personal, Other, not specified: AstraZeneca; Financial Interests, Personal, Other, not specified: Roche; Non-Financial Interests, Personal, Other, not specified: Roche; Financial Interests, Personal, Other, not specified: Eisai; Non-Financial Interests, Personal, Other, not specified: Eisai; Financial Interests, Personal, Other, not specified: MSD; Financial Interests, Personal, Other, not specified: Inivata. G.S. Sonke: Financial Interests, Institutional, Other, Institutional reimbursement for patient accrual: Novartis; Financial Interests, Institutional, Other, Institutional reimbursement for education and steering committee activities: Novartis; Non-Financial Interests, Institutional, Other, Institutional research support: Merck; Non-Financial Interests, Institutional, Other, Institutional research support: AstraZeneca; Non-Financial Interests, Institutional, Other, Institutional research support: Roche. L. Hart: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis. M. Campone: Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly. K. Petrakova: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: BMS. E.P. Winer: Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Tessaro; Financial Interests, Personal, Advisory Board: Leap; Financial Interests, Institutional, Research Grant, Research funding (institution): Merck; Financial Interests, Institutional, Research Grant, Research funding (institution): Genentech. W. Janni: Financial Interests, Personal and Institutional, Research Grant: Novartis. P.F. Conte: Financial Interests, Personal, Writing Engagements: Novartis. D. Cameron: Financial Interests, Institutional, Advisory Board, Institution reimbursed for my time on advisory boards: Novartis; Financial Interests, Institutional, Advisory Board, Institution reimbursed for my time on advisory boards: Pfizer; Financial Interests, Institutional, Other, Institution reimbursed for my time on an IDMC: Lilly. F. André: Financial Interests, Institutional, Funding, Research funding (institution): AstraZeneca; Financial Interests, Institutional, Funding, Research funding (institution): Lilly; Financial Interests, Institutional, Funding, Research funding (institution): Novartis; Financial Interests, Institutional, Funding, Research funding (institution): Pfizer; Financial Interests, Institutional, Funding, Research funding (institution): Roche. C. Arteaga: Financial Interests, Institutional, Research Grant, Research funding: Pfizer; Financial Interests, Institutional, Research Grant, Research funding: Lilly; Financial Interests, Institutional, Research Grant, Research funding: Takeda; Financial Interests, Institutional, Research Grant, Research funding: Radius; Financial Interests, Institutional, Research Grant, Research funding: PUMA Technology; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Symphogen; Financial Interests, Personal, Advisory Board: TAIHO Oncology; Financial Interests, Personal, Advisory Board: PUMA Technology; Financial Interests, Personal, Advisory Board: RADIUS; Financial Interests, Personal, Advisory Board: H3Biomedicine; Financial Interests, Personal, Advisory Board: OrigiMed; Financial Interests, Personal, Advisory Board: Daiichi Sankyo. J.P. Zarate: 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 and Institutional, Stocks/Shares: Novartis. T. Taran: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. F. Le Gac: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. P. Serra: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Novartis; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Lilly; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Merck; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Seattle Genetics.