391P - Real-world activity of sacituzumab govitecan for metastatic breast cancer

Background

Sacituzumab govitecan (SG) is an anti-Trop2 antibody-drug conjugate (ADC) approved for patients (pts) with HER2-negative metastatic breast cancer (MBC). Limited data are available about real-world activity of SG.

Methods

We included pts with MBC receiving SG at Dana-Farber Cancer Institute between 6/2014 - 1/2023 with ≥3 months (mo) of follow-up from SG start. We analyzed clinicopathological features and treatment patterns. We determined time to next treatment (TTNT), defined as time from SG start to initiation of next treatment or death, and overall survival (OS).

Results

We identified 184 pts: 121 with triple-negative (TNBC), 59 with hormone receptor-positive (HR+) BC, and 4 with HER2+ BC at time of SG start. Median age was 53.3 (25.4-73.9) years. Visceral disease was present in 75% of pts (70% in TNBC and 83% in HR+ BC). Brain/CNS metastases were identified in 43 pts (26% of TNBC and 19% of HR+ MBC). A total of 77 pts (35% of TNBC and 54% of HR+) had HER2-low BC at any timepoint before SG start. Median time from MBC diagnosis to SG start was 16 (1-148) mo for TNBC and 34 (1-217) mo for HR+ BC pts. Pts with TNBC received a median of 3 (0-9) prior lines for MBC, including chemotherapy (CT) (91%, median of 2 prior lines), immunotherapy (IO) (53%) and T-DXd (3%). Pts with HR+ BC received a median of 5 (0-14) prior lines for MBC, including CT (97%, median of 3 prior lines), CDK4/6 inhibitors (78%), IO (25%) and T-DXd (17%). With a median follow-up for survival of 23.6 mo, 112 TTNT and 86 OS events occurred in TNBC pts. Median TTNT was 4.3 (95% CI 3.7-5.0) mo. Most pts received CT alone (n=56, 64%), T-DXd (n=10, 11%) or IO-based (n=10, 11%) immediately after SG. Median OS was 10.4 (95% CI 8.0-13.3) mo. After a median follow-up for survival of 21.4 mo, 51 TTNT and 41 OS events occurred in HR+ BC pts. Median TTNT was 4.2 (95% CI 2.8-4.9) mo. Most pts (n=22, 63%) received CT alone immediately after SG, 3 pts received T-DXd. Median OS was 10.2 (95% CI 7.0-12.6) mo. Genomic features and gene expression data from circulating tumor DNA will be presented.

Conclusions

In this single-center observational experience of heavily pretreated pts with MBC, OS from SG start was < 1 year. There is urgent need for better treatment options in the post-ADC setting. Ongoing work is investigating biomarkers of response and resistance to SG.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Morganti: Other, expenses: AstraZeneca, Menarini. F. Brasó-Maristany: Financial Interests, Personal, Full or part-time Employment, part time employment: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: EP23382703 and EP23383369.: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: PCT/EP2022/086493, PCT/EP2023/060810: Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer. 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. T. Grinda: Financial Interests, Personal, Writing Engagement: Cancérologie Pratique; Financial Interests, Personal, Invited Speaker: Gilead, Pfizer; Financial Interests, Personal, Other, Personal Grant: Foundation Philippe. A.C. Garrido-Castro: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Novartis; 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. H. Parsons: Financial Interests, Institutional, Research Funding: Merck, Seagen; Financial Interests, Personal, Speaker, Consultant, Advisor: Caris, Guardant, AstraZeneca, Daiichi Sankyo. S. Sammons: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Foundation Medicine, Daichii Sankyo, Sermonix, Pfizer, Inc., Gilead; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Eli Lilly; Financial Interests, Institutional, Local PI: Sermonix; Financial Interests, Coordinating PI: Seagen. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; 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, 1TRIALSP, S.L.; 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, Local PI: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Steering Committee Member: Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Novartis; 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. 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, Advisory Board: Eisa; 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, Daichii 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. A. Giordano: Financial Interests, Personal, Advisory Board: Pfizer. All other authors have declared no conflicts of interest.