213P - Sequencing antibody-drug conjugates (ADCs) in patients (pts) with HER2-negative (HER2-) metastatic breast cancer (mBC)

Background

ADCs are effective for pts with HER2- MBC but little is known about sequencing of different ADCs.

Methods

We analyzed data from pts with HER2- MBC who received ≥2 ADCs and had ≥6 months (mo) follow-up at Dana-Farber Cancer Institute between 6/2014-1/2023. ADCs were grouped based on targets (HER2, Trop2, other) and payloads (topoisomerase inhibitor – TOPi; microtubule inhibitor - MI). We determined time to next treatment (tx) (TTNT) for ADC1, for the tx given immediately after ADC1 (postADC1), and for ADC2. TTNT-postADC1 was compared between pts who received consecutive ADCs or intervening tx between ADCs using an inverse probability weighting to account for non-randomized tx (adjustment for hormone receptor (HR)/HER2 IHC status at ADC1 start, year of ADC1 start, visceral disease at ADC1 start, TTNT-ADC1).

Results

We identified a total of 62 pts. Median age at MBC diagnosis was 51 (41-58) years. At ADC1 start, 29 pts (47%) had triple negative (TN) (17 HER2 low) and 33 (53%) pts had HR+ (21 HER2 low) MBC. A median of 1 (0-5) line of chemotherapy (CT) for MBC was given prior to ADC1 to both TN and HR+ MBC pts. Seven pts switched HER2 IHC status between ADC1 and ADC2 (3 from 0 to low, 4 from low to 0). Distribution of ADC1 was: 64% antiTrop2-TOPi, 23% antiHER2-TOPi, 13% nonHER2/nonTrop2-MI; for ADC2: 66% antiHER2-TOPi, 31% antiTrop2-TOPi, 3% nonHER2/nonTrop2-MI. The table reports TTNT for ADC1 and ADC2. A total of 26 pts had consecutive ADCs, while 36 pts had 1-5 intervening tx (median of 1 CT line, range 0-5) between ADCs. Median TTNT-postADC1 was 4.37 mo (95%CI 3.12-4.89) and did not differ if the postADC1 was another ADC or a different tx (HR 0.89, 95% CI 0.43-1.87, p=0.76). Genomic features and gene expression data from circulating tumor DNA (DNADX) will be presented. Table: 213P

Median TTNT for ADC1 and ADC2

Conclusions

In this cohort, most pts received antiTrop2 as ADC1 and antiHER2 as ADC2. Similar TTNT was observed with ADC1 and ADC2, irrespective of receptor status. Ongoing work is investigating biomarkers to guide tx sequencing.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Morganti: Other, expenses: AstraZeneca, Menarini. 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. A.C. Garrido-Castro: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Funding, Research funding: AstraZeneca, Daiichi Sankyo, Gilead Sciences, Merck, Zenith Epigenetics, Bristol Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; Other support (travel, accommodations, expenses): Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, Merck. A. Giordano: Financial Interests, Personal, Advisory Board: Pfizer. H.A. Parsons: Financial Interests, Institutional, Funding: Merck, Seagen; Financial Interests, Personal, Other, Advisory/Consultant: Caris, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: Guardant. A. Prat: Financial Interests, Personal, Invited Speaker: Roche, 1TRIALSP, S.L.; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca, Reveal Genomics; Financial Interests, Personal, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Royalties: Reveal Genomics, International Oncology Bureau, S.L., ; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Funding: Reveal Genomics; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA; Non-Financial Interests, Personal, Other, Research Foundation that gives grants to researchers: FERO. N.U. Lin: Financial Interests, Personal, Advisory Board, Ad board participation: Seattle Genetics, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Ad board/Steering Committee participation; consultant: AstraZeneca; Financial Interests, Personal, Advisory Board, Ad board/Steering committee participation; travel support: Olema Pharmaceuticals; Financial Interests, Personal, Other, Consultant: Blueprint Medicines, Janssen; Financial Interests, Personal, Other, High level Consulting: Artera Inc.; Financial Interests, Personal, Other, Steering committee: Stemline/Menarini; Financial Interests, Personal, Royalties, Royalties for book chapter(s): Up to Date; Financial Interests, Institutional, Funding, Trial funding to institute (and steering committee): Olema Pharmaceuticals, AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Funding, Trial funding to institute: Zion Pharmaceuticals; Financial Interests, Institutional, Funding, trial funding to institute: Pfizer, Genentech. 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; 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. All other authors have declared no conflicts of interest.