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

Background

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.

Methods

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.

Results

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.

Conclusions

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: 277P

^aData reported as Grade ≥3.

Clinical trial identification

CLEE011A2301, CLEE011F2301, CLEE011E2301, CLEE011O12301C, CLEE011A2404.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Safiyya Ali, MSc, CMPP of Nucleus Global.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Seagen, Art Tempi, Onkowissen, Medscape, Gilead, Sanofi, Zuelligpharma, Viatris; Financial Interests, Personal, Other, IDMC: Roche; Financial Interests, Personal, Advisory Board: Sandoz-Hexal, Seagen, Aptitude Health, Pfizer, Gilead, Sanofi; Financial Interests, Personal, Other, Husband: WSG (Husband); Financial Interests, Personal, Ownership Interest: West German Study Group; Financial Interests, Institutional, Funding: AstraZeneca, BMS, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Palleos, Seagen, TRIO, WSG; Non-Financial Interests, Member, Member German AGO Breast Guideline Committee: AGO Breast Committee; Non-Financial Interests, Member, Breast Cancer Educational Programs: ESO/ESCO; Other, Founding Editor: BreastCare Journal. W. Jacot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Novartis, Roche, Pfizer, Eli Lilly, MSD, BMS, Chugai, Seagen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory Board: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Invited Speaker: Roche, Roche, Novartis, Daiichi Sankyo, Daiichi Sankyo. M. Bellet Ezquerra: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Lilly, Stemline-Menarini; Other, Speaker'sBureau and Travel Expenses: Pfizer; Other, Speaker's Bureau: Novartis, Lilly. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad board participant/consultant: ARC Therapeutics, Daiichi Sankyo, Eisai, Genentech/Roche, Gilead, Novartis, Sanofi, Seagen; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Personal, Advisory Board, Ad board participation: Artios, Incyte Corp, BeyondSprings; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Advisory Board participation: Bayer, Infinity Therapeutics, Myovant, OncXerna, Umoja Biopharma, Zentalis, Zetagen, Natera; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Mersana Therapeutics; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory board/consulting: Jazz Pharma; Financial Interests, Institutional, Funding, and steering committing: AstraZeneca; Financial Interests, Institutional, Funding, and steering committee: Eli Lilly; Financial Interests, Institutional, Funding: Pfizer, Sanofi, Seagen, Odonate, Cyclacel, Exelixis, Bristol Myers Squibb, Eisai, Merck, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: CytomX; Financial Interests, Institutional, Funding, and steering committee: Gilead, Genentech/Roche; Financial Interests, Institutional, Invited Speaker: Stemline/Menarini. 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