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Mini Oral session 1

3MO - Analysis of germline BRCA1/2 mutations and uncommon somatic alterations from patients with HR+, HER2-, node-positive, high-risk early breast cancer enrolled in monarchE

Date

16 May 2024

Session

Mini Oral session 1

Topics

Translational Research

Tumour Site

Breast Cancer

Presenters

Christine Desmedt

Citation

Annals of Oncology (2024) 9 (suppl_4): 1-34. 10.1016/esmoop/esmoop103010

Authors

C. Desmedt1, N. Turner2, C. Arteaga3, H. Sasano4, S.L. Graff5, S. Loi6, M.P. Goetz7, D. Liu8, V.S. Rodrik-Outmezguine9, A.N. Sireci8, C.S. Rubenstein8, H. Won8, L. Litchfield10, M. Muñoz8, S. Chandarlapaty11

Author affiliations

  • 1 UZ Leuven - University Hospitals Leuven - Campus Gasthuisberg, Leuven/BE
  • 2 The Royal Marsden Hospital - Chelsea, London/GB
  • 3 UTSW - University of Texas Southwestern Medical Center, Dallas/US
  • 4 Tohoku University Hospital, Sendai/JP
  • 5 Warren Alpert Medical School of Brown University, Providence/US
  • 6 Peter MacCallum Cancer Centre, Melbourne/AU
  • 7 Mayo Clinic, Rochester/US
  • 8 Eli Lilly and Company, Indianapolis/US
  • 9 Loxo@Lilly, Indianapolis/US
  • 10 Eli Lilly and Company, 46285 - Indianapolis/US
  • 11 MSKCC - Memorial Sloan Kettering Cancer Center, New York/US

Resources

This content is available to ESMO members and event participants.

Abstract 3MO

Background

In monarchE (NCT03155997), 2 years of adjuvant abemaciclib + endocrine therapy (ET) resulted in sustained improvement in invasive disease-free survival (IDFS; HR=0.680, 7.6% absolute benefit at 5 years) in patients (pts) with HR+, HER2-, node-positive, high-risk early breast cancer (EBC). Considering multiple adjuvant options are available for EBC pts with germline BRCA1/2 mutations, we are reporting the exploratory results of pathogenic germline BRCA1/2 mutations (gBRCA1/2) as well as uncommon (incidence between ≥3% and <9%) somatic alterations from monarchE.

Methods

The whole exome sequencing (WES) biomarker sub-cohort (n=1173, 21% of ITT population) included a stratified random sample of pts from the ITT population plus all pts with IDFS events at the primary outcome data cut. Blood and tissue samples were evaluated for gBRCA1/2 and uncommon oncogenic alterations.

Results

At 54 months median follow up, 992 IDFS events (17.6%) were observed in the ITT population (n=5637) and 292 IDFS events (24.9%) were observed in the WES cohort (n=1173; abemaciclib+ET n=580; ET n=593). In the WES cohort, 3.5% (n=41, abemaciclib+ET n=20; ET n=21) had a gBRCA1/2 (BRCA1 n=6, BRCA2 n=35). In pts with gBRCA1/2, 1 (5%) experienced an IDFS event in the abemaciclib+ET arm, compared to 9 (42.8%) in the ET arm. Uncommon somatic alterations were detected in the following genes: CCNE2 (8.3%), PTEN (8.1%), AKT1 (6.0%), RB1 (5.6%), NF1 (5.5%), and BRCA2 (4.2%) and the IDFS event rates for pts with these alterations are reported in the table. Table: 3MO

Germline mutations
Total biomarker cohort (n=1173) Abemaciclib + ET (n=580) ET Alone (n=593)
Altered Gene N (%) N IDFS Events (%) N IDFS Events (%)
gBRCA1 6 (0.5%) 3 0 (0.0%) 3 3 (100.0%)
gBRCA2 35 (3.0%) 17 1 (5.9%) 18 6 (33.3%)
gBRCA1/2 41 (3.5%) 20 1 (5.0%) 21 9 (42.9%)
Uncommon somatic alterations
Prevalence Abemaciclib + ET ET Alone
Altered Gene N (%) N IDFS Events (%) N IDFS Events (%)
CCNE2 97 (8.3%) 49 18 (36.7%) 48 18 (37.5%)
PTEN 95 (8.1%) 40 14 (35.0%) 55 17 (30.9%)
AKT1 70 (6.0%) 32 8 (25.0%) 38 12 (31.6%)
RB1 66 (5.6%) 34 12 (35.3%) 32 7 (21.9%)
NF1 65 (5.5%) 35 8 (22.9%) 30 12 (40.0%)
BRCA2 49 (4.2%) 22 7 (31.8%) 27 8 (29.6%)

Conclusions

In these exploratory analyses from an IDFS-event-enriched cohort of monarchE, fewer IDFS events occurred in pts with germline BRCA1/2 mutations receiving adjuvant abemaciclib + ET compared to ET alone; however, small pt numbers limit the evaluation of statistical significance for both gBRCA1/2 and uncommon somatic alterations.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Medical writing and editorial support were provided by Carina Collins, an employee of Eli Lilly and Company.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

N. Turner: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Roche/Genentech, GSK, Zentalis pharmaceuticals, Repare therapeutics, GSK, Relay therapeutics, Gilead, Inivata, Guardant, Exact Sciences; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer, Roche/Genentech, Merck Sharpe and Dohme, Invitae, Inivata, Personalis, Natera; Financial Interests, Institutional, Other, provision of materials: BioRad; Financial Interests, Institutional, Other, Provision of assays: Guardant Health. C. Arteaga: Non-Financial Interests, Personal, Advisory Role, Scientific Advisor: Novartis, Merck, Eli Lilly and Company, AstraZeneca, Daiichi Sankyo, Sanofi, Taiho Oncology, PUMA Biotechnology, Arvinas, OrigiMed, Susan G. Komen; Financial Interests, Personal, Research Grant: Pfizer, Eli Lilly and Company, Takeda. S.L. Graff: Financial Interests, Personal, Advisory Board: Pfizer, Seagen, Novartis, AstraZeneca, Genentech, Lilly, Gilead Sciences, Daiichi Sankyo, Menarini; Financial Interests, Personal, Invited Speaker: The Academy for Healthcare Learning, DAVA Oncology, MJH Life Sciences, MedPage Today, MedIQ, Medical Educator Consortium; Financial Interests, Personal, Stocks/Shares: HCA Healthcare. S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech, Pfizer, Seattle Genetics; Financial Interests, Institutional, Advisory Board, Consultant: Novartis, GSK, Roche Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics; Financial Interests, Institutional, Expert Testimony, Consultant: PUMA Biotechnologies, BMS; Financial Interests, Institutional, Expert Testimony, consultant: Gilead Therapeutics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly; Financial Interests, Institutional, Funding, Research: Novartis, BMS, Merck, PUMA Biotechnology, Eli Lilly, Nektar Therapeutics, AstraZeneca, Seattle Genetics, Roche - Genentech; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Roche Genentech; Non-Financial Interests, Advisory Role, consultant (not compensated): Eli Lilly, Pfizer, Gilead Therapeutics. M.P. Goetz: Financial Interests, Institutional, Advisory Board: ARC Therapeutics, Biotheranostics, Blueprint Medicines, Rna Diagnostics, Sanofi Genzyme; Financial Interests, Institutional, Other, Consulting: AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Other, General Consulting: Lilly; Financial Interests, Personal, Invited Speaker, CME Activity: Research to Practice, Clinical Education Alliance, Medscape, MJH Life Sciences; Financial Interests, Personal, Invited Speaker, CME Panel Discussant: Total Health Conferencing; Financial Interests, Personal, Other, Moderator for CME Activity: Curio Science; Financial Interests, Institutional, Invited Speaker: Lilly, Pfizer, Loxo, Atossa Therapeutics, AstraZeneca, Sermonix. D. Liu, V.S. Rodrik-Outmezguine, C.S. Rubenstein, H. Won: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. A.N. Sireci: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Co; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Co; Non-Financial Interests, Advisory Role: Aster Insights, Biocartis. L. Litchfield: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. M. Muñoz: Financial Interests, Personal, Full or part-time Employment, I am a full time employee of Eli Lilly & Company: Eli Lilly & Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly & Company. S. Chandarlapaty: Financial Interests, Personal, Advisory Board: Lilly, Novartis, AstraZeneca, Effector, Nuvalent, Genesis Therapeutics, Prelude Therapeutics, SAGA Diagnostics, Neogenomics; Financial Interests, Personal, Stocks/Shares, Company with PI3K inhibitor asset - will not be discussed at all in the conference: Totus Medicines; Financial Interests, Personal, Ownership Interest, Work of this startup will not be discussed at all at the Congress: Odyssey Biosciences; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Paige.ai, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Lilly; Non-Financial Interests, Advisory Role: Breast Cancer Research Foundation. All other authors have declared no conflicts of interest.

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