342MO - Metastatic hormone receptor-positive breast cancer outcomes in 628 patients with BRCA1, BRCA2, or PALB2 pathogenic variants: Real-world data analysis of genomics and targeted therapy sequencing

Background

Patients with hormone receptor-positive metastatic breast cancer (HR+MBC) and pathogenic variants in BRCA1, BRCA2 or PALB2 (mBRCA+) are candidates for many targeted therapies. Data supports first-line CDK4/6 inhibitors (CDK4/6i), and poly (ADP-ribose) polymerase inhibitors (PARPi) as most effective in earlier lines of therapy. However, scant data supports optimal sequence. Therefore, we compared patients w/HR+MBC and mBRCA+ treated w/CDK4/6i and/or PARPi and associated genomic signatures.

Methods

11,650 HR+MBC pts underwent DNA/RNA seq at Caris Life Sciences, w/somatic testing performed. HR+ defined by IHC per ASCO/CAP definition. Outcomes data was obtained from insurance claims and calculated from first contact to last of treatment time (OS) and first to last treatment (PFS).

Results

628 pts were identified w/ both HR+MBC and mBRCA+ (median age: 57 years; range 23-90+; 96% Female, 4% Male). mBRCA+ variants: BRCA2 66%, BRCA1 19%, and PALB2 15%. Overall, mBRCA+ HR+MBC had poor prognosis vs wtBRCA HR+MBC, incl. when treated w/CDK4/6i (PFS 9.5 m vs 10.9 m, HR=1.25 95%CI 1.10-1.42; p

Conclusions

Among pts w/HR+MBC and mBRCA+, more prospective analysis is needed to evaluate optimal targeted therapy sequencing, establish germline status of mBRCA+ variants, and include consideration for PIK3CA status/targeting.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G. Parkinson: Financial Interests, Institutional, Research Grant: Color Health Foundation; Non-Financial Interests, Leadership Role: Caribbean Alliance to Control and Prevent Cancer Inc. M. Lustberg: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Gilead; Financial Interests, Personal, Invited Speaker: Loxo Lilly; Financial Interests, Personal, Other, consultant: Pfizer. S. Nazari: Financial Interests, Personal, Full or part-time Employment: Caris Life Sciences; Financial Interests, Personal, Stocks/Shares: Caris Life Sciences. A. Elliott: Financial Interests, Personal, Full or part-time Employment: Caris Life Sciences. G. Sledge: Financial Interests, Personal, Leadership Role: Caris. R. Jeselsohn: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Astra Zenenca, Novartis, Carrick Therapeutics; Financial Interests, Institutional, Funding: Lilly, Pfizer. R.W. Sobol: Financial Interests, Institutional, Stocks/Shares, Share holder: Pfizer. A. Sandoval-Leon: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Merck, Gilead, Sanofi, Stemline; Financial Interests, Institutional, Local PI: AstraZeneca, OBI; Financial Interests, Personal, Local PI: Merck. R. Gopalakrishnan: Financial Interests, Institutional, Research Grant: Conquer Cancer Foundation. L.E. Nye: Financial Interests, Personal, Advisory Board: Myriad. A. Kurian: Financial Interests, Institutional, Research Grant, Research funding to my institution for an investigator-initiated study, 2017-2019: Myriad Genetics; Non-Financial Interests, Other, Collaborative research, no funding: Invitae, Merck, Ambry Genetics, Color Health, GeneDx, Foundation, Gilead. F. Lynce: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi, Eli Lilly, Pfizer; Financial Interests, Personal, Officer, Executive Officer: Alliance Foundation Trials; Financial Interests, Institutional, Local PI: Gilead, AstraZeneca, Ideaya; Financial Interests, Personal, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Coordinating PI: Zentalis, Merck. S. 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, MedIQ, Medical Educator Consortium, IntegrityCE, Research to Practice; Financial Interests, Personal, Writing Engagement: MedPage Today, WebMD/Medscape; Financial Interests, Personal, Full or part-time Employment: Dr Susan Love Foundation for Breast Cancer Research; Financial Interests, Personal, Stocks/Shares: HCA Healthcare; Financial Interests, Personal and Institutional, Steering Committee Member: Daiichi Sankyo, Novartis, AstraZeneca. All other authors have declared no conflicts of interest.