LBA18 - Final overall survival (OS) for abemaciclib plus trastuzumab +/- fulvestrant versus trastuzumab plus chemotherapy in patients with HR+, HER2+ advanced breast cancer (monarcHER): A randomized, open-label, phase II trial

Background

Abemaciclib, an oral, selective CDK4 & 6 inhibitor, significantly improved PFS in HR+, HER2+ advanced breast cancer (ABC; locoregionally recurrent or metastatic) when combined with fulvestrant and trastuzumab, compared to trastuzumab plus chemotherapy in monarcHER (Tolaney 2020, Lancet Oncol.) Here, we report the OS results at the prespecified final analysis.

Methods

monarcHER (NCT02675231) is a randomized, multicenter, open-label phase 2 trial. Randomization was 1:1:1 to arm A (abemaciclib 150mg PO BID, trastuzumab IV, fulvestrant 500mg IM), arm B (abemaciclib, trastuzumab), and arm C (trastuzumab, SOC chemotherapy). Stratification factors were number of prior systemic regimens for ABC and measurable disease. Exploratory biomarker analyses were also conducted, including evaluation of intrinsic subtypes by RNAseq.

Results

At the time of data cutoff (31 Mar 2022), of the 237 patients enrolled, 157 deaths had occurred across the treatment arms, 50 deaths (63%) arm A, 54 deaths (68%) arm B, and 53 deaths (67%) arm C. Median follow-up was 52.9 months. mOS was 30.3 months in arm A, 31.43 months in arm B and 22.7 months in arm C (A v C: HR 0.75 [95% CI 0.47, 1.21]; nominal 2-sided p-value 0.243; B v C: HR 0.73 [95% CI 0.46, 1.15]; nominal 2-sided p-value 0.177). In exploratory RNAseq analyses, luminal subtypes were associated with longer PFS (8.6 v 5.4 months [HR 0.54, 95% CI 0.38, 0.79]) and OS (31.7 v. 19.7 months [HR 0.68, 95% CI 0.46, 1]) compared to non-luminal. Updated PFS and safety findings were consistent with the primary analysis (data cutoff 8 Apr 2019).

Conclusions

Abemaciclib plus trastuzumab ± fulvestrant numerically improved OS in women with HR+, HER2+ ABC compared to chemotherapy plus trastuzumab with a manageable safety profile.

Clinical trial identification

NCT02675231.

Editorial acknowledgement

Medical writing support was provided by Trish Huynh and Nicholas Pulliam, employees of Eli Lilly and Company.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

F. André: Financial Interests, Institutional, Research Grant: Roche, Eli Lilly and Company, Pfizer, Novartis, Daiichi Sankyo, AstraZeneca. H. Denys: Other, Institutional, Advisory Board: Pfizer, Roche, PharmaMar, AstraZeneca, Eli Lilly and Company, Novartis, Amgen, GSK, Seagen; Other, Institutional, Other, Travel, Accomodations, Expenses: Pfizer, Roche, PharmaMar, Teva, AstraZeneca. S. Goel: Other, Advisory Board: Eli Lilly and Company, Pfizer; Other, Research Grant, Lab research funding: Eli Lilly and Company, G1 Therapeutics. L.M. Litchfield: Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. A. Appiah: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. Y. Chen: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. S.M. Tolaney: Financial Interests, Personal, Principal Investigator, Institutional Research Funds; honorarium: AstraZeneca, Eli Lilly and Company, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Gilead, Exelixis, Bristol Myers Squibb, Eisai, Nanostring, Sanofi; Financial Interests, Personal, Advisory Board, Institutional Research Funds; honorarium: AstraZeneca, Eli Lilly and Company, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Bristol Myers Squibb, Eisai, Nanostring, Sanofi; Financial Interests, Personal, Other, Steering Committee, Institutional Research Funds; honorarium: Eli Lilly and Company; Financial Interests, Personal, Advisory Role, Institutional Research Funds; honorarium: Gilead; Financial Interests, Personal, Advisory Board, Honorarium: Puma, Oncopep, Kyowa Kirin Pharmaceuticals, Samsung Bioepsis Inc., Mersana Therapeutics, Ellipses Pharma, 4D Pharm, OncoSec Medical Incorporated, BeyondSpring Pharmaceuticals, Zymeworks, Zentalis, Reveal Genomics, ARC Therapeutics; Financial Interests, Personal, Principal Investigator, Institutional Research Funds: Cyclacel, Odonate; Financial Interests, Personal, Other, Consultant/Steering Committee: Odonate; Financial Interests, Personal, Principal Investigator, Consultant; Institutional Research Funds; honorarium: Seattle Genetics; Financial Interests, Personal, Other, Consultant; honorarium: Daiichi Sankyo, Athenex; Financial Interests, Personal, Other, Consulting/honorarium: Oncopep; Financial Interests, Personal, Other, Steering Committee/Consultant; Honorarium: CytomX; Financial Interests, Personal, Other, Honorarium: Chugai Pharmaceuticals, OncXerna, Zetagen; Financial Interests, Personal, Other, Consulting/Honorarium: Blueprint Medicines. All other authors have declared no conflicts of interest.