176P - ERBB2 amplifications across sex, race, and cancer types

Background

Fam-trastuzumab deruxtecan-nxki was granted accelerated approval for patients with any advanced HER2-positive cancer. Since ERBB2 amplification status is concordant with HER2 overexpression and IHC positivity (Dumbrava et al. JCO PO. 2019), we sought to examine the distribution of ERBB2 amplifications across sex, race, and cancer type subgroups in a large dataset.

Methods

This study included 103,786 patients with genomic tumor profiling data in the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry. Clinical characteristics were compared using Chi-squared and Mann–Whitney U tests. FDR-adjusted Q-values were determined by the Benjamini–Hochberg method.

Results

Our cohort included 79.6% self-identified White, 6% Asian, and 5.7% Black patients. Most samples (63%) originated from primary tumors. ERBB2 amplifications were identified in 4.02% (5,040) of samples, most frequently in esophageal adenocarcinomas (19.4%; 217/1,119), breast cancer (12%; 1,346/11,209), salivary gland cancer (7.2%; 43/600), bladder cancer (6.1%; 245/4,012), and endometrial cancer (4.7%; 204/4,328). Male patients with esophagogastric cancer had a significantly higher enrichment with ERBB2 amplifications than female patients (14.8%; 414/2,793 vs. 9.5%; 102/1,073) (OR=1.66; Q<0.001). Differences according to race were also identified: a higher rate of ERBB2 amplifications was found among Asian vs. White and Black patients with bladder cancer (11.4%; 15/131 vs. 5.6%; 202/3,576) (OR=2.16; Q=0.048), and colorectal cancer (3.9%; 27/686 vs. 2.3%; 207/8,833) (OR=1.7; Q=0.048). Black patients with endometrial cancer had a significantly higher enrichment with ERBB2 amplifications compared to White patients (10.2%; 43/422 vs. 3.8%; 126/3,271) (OR = 2.83; Q<0.0001). Finally, a higher rate of ERBB2 amplifications was found in metastases vs. primary tumors in patients with hepatobiliary cancer (5.5%; 35/642 vs. 2.4%; 41/1,720) (OR=2.36; Q=0.008) and esophagogastric cancer (16%; 147/917 vs. 12.4%; 360/2,898) (OR=1.34; Q=0.015).

Conclusions

This study illustrates differences in the distribution of ERBB2 amplifications across sex, race, and cancer types and may guide treatment selection with HER2-directed therapies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Saad: Financial Interests, Personal, Invited Speaker: Roche Genentech. M. Pomerantz: Financial Interests, Personal, Invited Speaker: Bayer. R.R. McKay: Financial Interests, Personal, Advisory Board: Aveo, AstraZeneca, Bayer, Calithera, Dendreon, Exelixis, JNJ, Merck, Pfizer, Sanofi, Tempus, BMS, Lilly, Sanofi, Seagen, Telix, Sorrento Therapeutics, Eisai, Blue Earth Diagnostics; Financial Interests, Personal, Other, Molecular tumor board: Caris; Financial Interests, Personal, Other, Consultant: Dendreon, Myovant; Financial Interests, Personal, Invited Speaker: Exelixis, Merck, Novartis, Pfizer; Financial Interests, Steering Committee Member: Aveo, Merck, Eli Lilly; Financial Interests, Local PI: JNJ, Seagen, Calibr, Poseida, Oncternal, Scholar Rock, Merck, Xencor, Genentech, Eli Lilly, BMS; Financial Interests, Trial Chair: Bayer, AstraZeneca; Financial Interests, Institutional, Local PI: Exelixis. P. Tarantino: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca, Daiichi Sankyo, Genentech, Eli Lilly, Gilead; Financial Interests, Institutional, Funding: AstraZeneca. D.A. Braun: Financial Interests, Personal, Invited Speaker, Speaker on innovation in oncology and clinical trial design: LM Education/Exchange Services; Financial Interests, Personal, Other, Consulting: Octane Global, Defined Health, ADepartment Field Solutions, Slingshot Insights, Blueprint Partnerships, Charles River Associates, Trinity Group, Insight Strategy, Catenion, PWW Consulting, Haymarket; Financial Interests, Personal, Advisory Board, Advisory Board: Exelixis, AVEO; Financial Interests, Personal, Invited Speaker: Aptitude Health, AbbVie, ASCO Post RCC Roundtable, Targeted Oncology, Pfizer, Medscape; Financial Interests, Personal, Other, Advisor: Fortress Biotech (subsidiary), DLA Piper; Financial Interests, Personal, Other, Co-Founder: CurIOS; Financial Interests, Personal, Advisory Board: Elephas Bio, Merck, Eisai, Compugen, Link Cell Therapies, Scholar Rock, Neomorph; Financial Interests, Personal, Other, Medical education: Accolade 2nd.MD; Financial Interests, Personal, Other, stock options: Elephas; Financial Interests, Personal, Research Grant: AstraZeneca, Exelixis; Non-Financial Interests, Advisory Role: Bristol Myers Squibb; Non-Financial Interests, Member: ASCO. 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, Hengrui USA; 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, Sumitovant Biopharmaceuticals, OncXerna, Umoja Biopharma, Zentalis, Natera; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb; 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, Personal, Advisory Board: Tango Therapeutics, Systimmune, eFFECTOR, Cullinan Oncology, Arvinas; 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, Steering Committee Member: CytomX; Financial Interests, Institutional, Funding, and steering committee: Gilead, Genentech/Roche; Financial Interests, Institutional, Local PI: Stemline/Menarini. T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; 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Financial Interests, Personal, Royalties, For writing and updating chapters in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National Chair: BMS, Merck, Exelixis, AstraZeneca, Takeda, Tracon; Financial Interests, Institutional, Local PI, National Chair: Roche; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Local PI: Surface Oncology, GSK; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: Alliance Cooperative Group; Financial Interests, Institutional, Research Grant, for GU oncology translational research through IION program: BMS; Financial Interests, Institutional, Research Grant, for GU oncology translational research: Exelixis; Financial Interests, Institutional, Research Grant, For Health outcomes research: Roche; Financial Interests, Institutional, Local PI, leads trials as PI: Nikang; Non-Financial Interests, Leadership Role, Co-Chair of the meeting, 2019- current and BOD member (unpaid): Kidney Cancer Research Summit of KidneyCAN; Non-Financial Interests, Principal Investigator, Trial Global and National PI with GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Track Leader/Session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Personal, Other, Speaker/Discussant/Track Leader: ESMO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med, Guardant, Invitae; Non-Financial Interests, Personal, Other, Grants reviewers: AACR; Non-Financial Interests, Personal, Other, Reviewer of papers: Various journals (e.g. NEJM, Lancet, JCO); Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g. ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, pharmagenesis, and others). However, first draft frequently initiated by myself when I am 1st author.: Medical Communication; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Other, Political vote usually as “independent”, not a member of any political party. I am an issue voter.: General US Politics; Other, Employee at DFCI. Please see https://www.dana-farber.org/ for mission statement (non-profit hospital). I am also the past President of Medical Staff at DFCI 2015-2018: Dana-Farber Cancer Institute (DFCI); Other, Professor at HMS, Please see https://hms.harvard.edu/ for mission statement (non-profit school): Harvard Medical School (HMS); Other, The institution filed patents related to biomarkers of immune checkpoint blockers, and circulating tumor DNA. No money made and some patents were abandoned.: Filed patents. All other authors have declared no conflicts of interest.