339P - Management of abemaciclib associated adverse events in patients with hormone receptor positive (HR+), HER2- advanced breast cancer: Analysis of the MONARCH trials

Abstract

Background: Abemaciclib is a CDK4 & 6 inhibitor dosed continuously with demonstrated efficacy and an acceptable safety profile in pts with HR+, HER2-negative advanced breast cancer as monotherapy (MONARCH 1) and in combination with endocrine therapy; with fulvestrant (MONARCH 2) or with non-steroidal aromatase inhibitors (MONARCH 3). The most frequent adverse event (AE) is low-grade diarrhea; neutropenia is the most frequent grade 3/4 AE. We describe the timing and management of common AEs in the MONARCH trials. Methods: Enrollment criteria, study designs and key eligibility criteria of MONARCH 1, 2 and 3 have been reported (Dickler et al. 2017; Sledge et al. 2017; Goetz et al. 2017). Pts were advised to initiate antidiarrheal therapy at first sign of diarrhea and notify the investigator, drink fluids. If not improved within 24 hours to < grade 1, treatment was suspended until diarrhea resolved. Dose reductions required for grade ≥3 or persistent grade 2 diarrhea. For grade 3 neutropenia, abemaciclib was held until < grade 2. The dose was reduced for recurrent grade 3 or grade 4 neutropenia. Results: Across MONARCH, the median time to onset of diarrhea was between day 6-8. First dose reductions for diarrhea occurred at a median of 28-41 days. Dose holds for diarrhea were brief, constituting 1.7-3.8% off total treatment time. The median time to onset of grade 3/4 neutropenia was 29-36.5 days, and resolved at a median of 11-15 days. AEs were managed by dose adjustments and/or supportive medication (Table).Table: 339PSummary of Dose Adjustments in Pts Experiencing Diarrhea or NeutropeniaCharacteristicsMONARCH 1 AbemaciclibMONARCH 2 Abemaciclib + FMONARCH 3 Abemaciclib + NSAIN = 132N = 441N = 327Diarrhea (any grade), n(%)119 (90.2)381 (86.4)269 (82.3)Grade 326 (19.7)59 (13.4)31 (9.5)Incidences per patient, n (%)160 (50.4)185 (48.6)124 (46.1)229 (24.4)90 (23.6)52 (19.3)≥330 (25.2)106 (27.8)93 (34.6)Outcome, number (%) of events263995802Not recovered/resolved15 (5.7)106 (10.7)70 (8.7)Treatment change, n (%)119381269Dose reduction of study drug27 (22.7)83 (21.8)45 (16.7)Dose omission32 (24.2)83 (21.8)51 (19.0)Treatment discontinuation1 (0.8)13 (3.4)6 (2.2)Antidiarrheal medication, n (%)80 (60.6)333 (75.5)226 (69.1)Neutropenia (any grade), N (%)49 (37.1)203 (46.0)143 (43.7)Grade ¾32 (24.2)117 (26.5)78 (23.9)Treatment change, n (%)Dose reduction of study drug14 (10.6)44 (10.0)42 (12.8)Dose omission21 (15.9)72 (16.3)57 (17.4)Treatment discontinuation07 (1.6)9 (2.8) Open table in a new tab Conclusions: The dose adjustment strategy used in the MONARCH studies was effective at managing AEs by dose adjustment and/or supportive medication. Understanding the safety profile of abemaciclib can inform AE management and can extend time on treatment. Clinical trial identification: NCT02102490 (MONARCH 1), NCT02107703 (MONARCH 2), NCT02246621 (MONARCH 3). Legal entity responsible for the study: Eli Lilly and Company. Funding: Eli Lilly and Company. Disclosure: H.S. Rugo: Grants/research support: GSK, Genentech/Roche, Novartis, Pfizer, Merck, Eisai, Plexxikon, Macrogenics, Lilly, OBI (all funding to UC Regents only). V. André, S. Barriga, T. Forrester: Employee and stakeholder: Eli Lilly and Company. M.P. Goetz: Consultant: Eli Lilly and Company, bioTheranostics, Novartis, Genomic Health, Eisai, Biovica, and Sermonix; Grant/Research support from Eli Lilly and Pfizer. All other authors have declared no conflicts of interest.