277P Descriptive analysis of hepatic safety for patients (pts) with HR+/HER2− breast cancer (BC) treated with ribociclib (RIB) + endocrine therapy (ET)

Transaminase elevations are a known adverse event (AE) of special interest with RIB + ET. Understanding the incidence, duration, and management of these AEs is critical for maximizing treatment benefit with RIB + ET. We present a descriptive analysis of liver enzyme elevations with RIB + ET across multiple trials. Data from phase III registrational and phase IIIb expanded population (representative of real-world) trials were evaluated, including pts with HR+/HER2− advanced BC treated with RIB 600 mg + ET in MONALEESA (ML)-2, -3, and -7 and COMPLEEMENT-1, and pts from NATALEE with HR+/HER2− early BC treated with RIB 400 mg + ET. Incidence, time to onset, duration, and management of liver enzyme elevations were evaluated across each trial. With RIB + ET, the rates of all-grade (G) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations ranged from 13% to 19%; events were mostly G1/2 (Table). ALT/AST elevations were identified by recommended monitoring (serial liver function tests) and occurred early in RIB treatment. Among pts with G≥3 events, median time to onset ranged from 2.6 to 4.9 mo for each trial and median duration ranged from 0.7 to 1.6 mo; these events resolved with the current dose modification guidelines. Cases of Hy's law occurred in ≤1% of pts and were effectively managed by discontinuing RIB; most cases (95%) were resolved or resolving within 2.1 to 17.5 mo of RIB discontinuation. Discontinuation of RIB due to ALT/AST elevations was consistent across trials and occurred in ≤7% of pts. A similar incidence of liver events across trials at both the RIB 600- and RIB 400-mg doses suggests that dose does not play a key causative role in these AEs. Overall, cases of liver enzyme elevation were generally low grade and manageable with recommended dose modification guidance; severe cases were rare and reversible after discontinuation of RIB.Table: 277Pn (%)ML-2 N=334ML-3 N=483ML-7 N=335NATALEE N=2525COMPLEEMENT-1 N=3246ALT elevationAll G52 (16)70 (14)43 (13)492 (19)526 (16)G3/431 (9)41 (8)18 (5)192 (8)249 (8)aAST elevationAll G50 (15)64 (13)40 (12)426 (17)459 (14)G3/419 (6)29 (6)12 (4)118 (5)184 (6)aHy's law4 (1)2 (<1)08 (<1)7 (<1)Discontinuation due to:ALT increased15 (4)22 (5)8 (2)180 (7)197 (6)AST increased9 (3)13 (3)5 (1)71 (3)129 (4)Dose interruption due to:ALT increased17 (5)38 (8)16 (5)255 (10)245 (8)AST increased12 (4)37 (8)11 (3)171 (7)209 (6)Dose adjustment due to:ALT increased10 (3)5 (1)5 (1)49 (2)50 (2)AST increased5 (1)6 (1)4 (1)16 (1)Not reportedaData reported as Grade ≥3. Open table in a new tab