Howard A Burris1, Arlene Chan2, Aditya Bardia3, J Thaddeus Beck4, Joohyuk Sohn5, Patrick Neven6, Debu Tripathy7, Seock-Ah Im8, Stephen Chia9, Francisco J Esteva10, Lowell Hart11, Juan Pablo Zarate12, Antonia Ridolfi13, Karen Rodriguez Lorenc12, Denise A Yardley14. 1. Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA. Howard.Burris@SarahCannon.com. 2. Breast Cancer Research Centre WA and Curtin University, Perth, Australia. 3. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. 4. Highlands Oncology Group, Fayetteville, AR, USA. 5. Severance Hospital, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea. 6. Multidisciplinary Breast Centre, Universitair Ziekenhuis Leuven, Leuven, Belgium. 7. The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 8. Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. 9. BC Cancer Agency, Vancouver, BC, Canada. 10. NYU Langone Health, New York, NY, USA. 11. Florida Cancer Specialists, Sarah Cannon Research Institute, Fort Myers, FL, USA. 12. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. 13. Novartis Pharmaceuticals Corporation, Paris, France. 14. Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA.
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.
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.
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