Safety and impact of dose reductions on efficacy in the randomised MONALEESA-2, -3 and -7 trials in hormone receptor-positive, HER2-negative advanced breast cancer

Abstract

Background: This pooled analysis of MONALEESA trials evaluated the safety of ribociclib plus endocrine therapy (RIB + ET) with a focus on dose reductions in first-line patients.

Methods: In the dose reduction analysis, data were pooled from MONALEESA-2 (all patients), MONALEESA-3 (patients receiving treatment as first-line ET) and MONALEESA-7 (patients receiving combination therapy with an NSAI as initial ET). Efficacy was analysed by ribociclib relative dose intensity (DI). Safety was analysed in all patients in the trials (except those receiving tamoxifen in MONALEESA-7) and those with/without ≥1 ribociclib dose reduction.

Results: Of 818 women who received first-line RIB + ET, 41.8% required ≥1 dose reduction due to AEs (most commonly, neutropenia). Median RIB relative DI in patients without and with dose reductions was 99.3% and 65.6% in MONALEESA-2, 98.4% and 67.8% in MONALEESA-3 and 98·0% and 66·3% in MONALEESA-7. Median PFS was 24.8, 24.9 and 29.6 months for patients who received ≤71% (30th percentile), 72-96% (60th percentile) and 97-100% (90th percentile) RIB relative DI, respectively. No new safety signals emerged in the pooled safety analysis.

Conclusions: This analysis provides reassuring data showing that the clinical benefit of RIB is preserved when dose modifications are undertaken to manage AEs.

Trial registration: MONALEESA-2 (NCT01958021) first posted October 8, 2013; MONALEESA-3 (NCT02422615) first posted April 21, 2015; MONALEESA-7 (NCT02278120) first posted October 29, 2014.

Conflict of interest statement

H.A.B. reports consulting or advisory for AstraZeneca, Bristol-Myers Squibb, FORMA Therapeutics, Janssen, MedImmune, Mersana, Novartis, Roche/Genentech, TG Therapeutics; grants from AbbVie, Agios, AstraZeneva, Bayer, BioMed Valley Discoveries, Boehringer Ingleheim, Bristol-Myers Squibb, Celgene, Celdex, CytomX Therapeutics, eFFECTOR Therapeutics, Gilead Sciences, GlaxoSmithKline, Immunocore, Incyte, Janssen, Jounce Therapeutics, Lilly, Loxo, Macrogenics, MedImmune, Merck, Mersana, Milennium, Moderna Therapeutics, Novartis, Pfizer, PTC Therapeutics, Roche/Genentech, Seattle Genetics, Takeda, Tarveda Therapeutics, Tesaro, TG Therapeutics, Valent Technologies, Vasastern, Vertex; A.C. has nothing to disclose; A.B. reports consulting or advisory for Immunomedics, Pfizer, Novartis, Genentech/Roche, Merck, Radius Health, Spectrum Pharma, Taiho Pharma, Biothernostics Inc., Sanofi, Daichi Pharma, Puma; personal fees from Biothernostics Inc., Pfizer, Novartis, Genentech/Roche, Merck, Radius Health, Immunomedics, Spectrum Pharma, Taiho Pharma, Sanofi, Daiichi Pharma, Puma; grants from Genentech/Roche, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Mersana, Innocrin, Biothernostics Inc.; J.T.B. has nothing to disclose; J.S. has nothing to disclose; P.N. has nothing to disclose; D.T. reports consulting or advisory for Novartis, Pfizer, Genomic Health, GlaxoSmithKline; personal fees from Novartis, Pfizer, Genomic Health, GlaxoSmithKline; research grant from Novartis; S.-A.I. reports consulting or advisory for AstraZeneca, Novartis, Hanmi, Pfizer, Eisai, Amgen, MediPacto, Genentech/Roche, Lilly; personal fees from AstraZeneca, Novartis, Hanmi, Pfizer, Eisai, Amgen, MediPacto, Genentech/Roche, Lilly; grants from AstraZeneca, Pfizer, Genentech/Roche; S.C. reports payment to his institution from Novartis for conduct of the clinical trial during the conduct of this study; advisory board: his institution received funds for participation in clinical trials by Novartis, Pfizer, Hoffman LaRoche, Eli Lilly; he is a subject editor for the British Journal of Cancer. F.J.E. reports consulting or advisory for Novartis, Pfizer, Genentech/Roche, Celltrion Healthcare, Seattle Genetics; personal fees from Novartis, Pfizer, Genentech/Roche, Celltrion Healthcare, Seattle Genetics; grants from Novartis, Pfizer, GlaxoSmithKline, Genentech/Roche; L.H. reports consulting or advisory for Novartis; personal fees from Novartis; grants from Novartis; J.P.Z. reports employment and stock ownership from Novartis; A.R. reports employment and stock ownership from Novartis; K.R.L. reports employment and stock ownership from Novartis; D.A.Y. reports consulting or advisory for Biothernostics Inc., Bristol Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Eisai, Genentech/Roche, NanoString Technologies, Novartis; personal fees from Biothernostics Inc., Bristol Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Eisai, Genentech/Roche, NanoString Technologies, Novartis; grants from Daiichi Sankyo, Lilly, Eisai, Novartis, Abbvie, AstraZeneca, Clovis Oncology, Immunomedics, InventisBio, Lilly, MedImmune, Medivation, Merck, Oncothyreon, Pfizer, Syndax, Tesaro.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Figures

Fig. 1. Progression-free survival according to ribociclib relative DI in patients receiving ribociclib with first-line endocrine treatment (FAS; investigator assessment)a.

DI dose intensity, FAS full analysis set. aPooled data: patients from MONALEESA-2 (ribociclib plus letrozole group), MONALEESA-3 (ribociclib plus fulvestrant group) and MONALEESA-7 (ribociclib plus non-steroidal aromatase inhibitor group).