RIB (cyclin-dependent kinase 4/6 inhibitor) + various ET partners demonstrated longer progression-free survival vs placebo (PBO) + ET in patients (pts) with HR+/HER2– ABC in the Phase III MONALEESA (ML) studies. Here we present a safety analysis of pooled data from ML-2, ML-3, and ML-7.
Postmenopausal pts with ABC were enrolled in ML-2 (ET-naive) and ML-3 (≤ 1 prior ET) to receive PBO or RIB + study-designated ET, letrozole (ML-2) or fulvestrant (ML-3). In ML-7 (ET-naive; ≤ 1 line of chemotherapy for ABC), premenopausal pts received RIB or PBO + goserelin + a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen (NSAI cohort only from ML-7 included here). Safety analyses included rate of associated RIB/PBO discontinuations and time to and duration of first event. Adverse events (AEs) were assessed via Common Terminology Criteria for AEs v4.03.
Data were pooled from 1883 pts in the safety set treated with RIB + ET (1065 pts) or PBO + ET (818 pts). Neutropenia and leukopenia were the most common all-grade exposure-adjusted AEs of special interest and the most common any-cause grade 3/4 AEs (≥10%). Fridericia’s corrected QT interval (QTcF) >480 ms occurred in 5% vs 1% of pts in the RIB vs PBO arms. A new QTcF >500 ms occurred in 1% vs < 1% of pts, respectively. In the RIB arm, the median time to first grade ≥2 event was 2 weeks for neutropenia and QT prolongation and 12 weeks for elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST). Median duration of these first events was 2-4 weeks. The rates of study treatment discontinuation due to AEs were 7% vs 3%, and the most common all-grade AEs that led to discontinuation were elevated ALT (4% vs < 1%) and elevated AST (2% vs 1%) in the RIB vs PBO arms, respectively.
|Exposure-adjusted any-grade AESI irrespective of causality, n (incidence rate per 100 patient-treatment years)||RIB + ET (n = 1065)||PBO + ET (n = 818)|
|Any AESI||992 (561.4)||543 (131.0)|
|Neutropeniaa||788 (196.6)||43 (5.1)|
|Leukopeniab||330 (34.9)||36 (4.2)|
|Anemiac||200 (18.2)||51 (5.9)|
|Increased ALT||161 (13.8)||48 (5.7)|
|Increased AST||150 (12.7)||51 (6.0)|
|Prolonged QT||69 (5.6)||13 (1.5)|
AESI, adverse event of special interest; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ET, endocrine therapy; PBO, placebo; RIB, ribociclib.a
Includes neutropenia, decreased neutrophil count, febrile neutropenia, granulocytopenia, and neutropenia sepsis.b
Includes leukopenia, decreased white blood cell count, lymphopenia, and decreased lymphocyte count.c
Includes anemia, decreased hemoglobin, macrocytic anemia, and decreased red blood cell count.
Addition of RIB to various ET partners demonstrated a consistent and manageable safety profile in pts with HR+/HER2– ABC.
MediTech Media, funded by Novartis.
Clinical trial identification
MONALEESA-2 (NCT01958021), MONALEESA-3 (NCT02422615), MONALEESA-7 (NCT02278120).
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Novartis Pharmaceuticals Corporation.
D. Tripathy: Grants, personal fees: Novartis during the conduct of the study; Personal fees: Pfizer during the conduct of the study; Personal fees: Nektar Therapeutics, CellMax Life, Sellas Life Sciences, Polyphor Ltd, GlaxoSmithKline, Genomic Health, outside the submitted work. G.N. Hortobagyi: The work under consideration for publication - Novartis: Grant and personal fees relevant financial activities outside the submitted work: Lily and Pfizer: Consulting. S-A. Im: Relevant financial activities outside the submitted work: AstraZeneca; Grant: Spectrum, Novartis, Roche/Genentech - Advisory board member. S. Chia: Honorarium for advisory boards: Novartis, Hoffmann-La Roche, Pfizer, AstraZeneca, Genomic Health; My institution has participated in research studies: Novartis, Hoffmann-La Roche, Pfizer, AstraZeneca, Genomic Health, Genentech, Merck, BMS. S.A. Hurvitz: Grants: Ambryx, Amgen, Bayer, OBI Pharma, Bimarin, Cascadian, Daiichi Sankyo, Dignitana, Genentech, GSK, Lilly, Macrogenics, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Pieris, Puma, Roche, Seattle Genetics. A. Ridolfi: Employee: Novartis Pharmaceuticals Corporation. All other authors have declared no conflicts of interest.