Background

The DESTINY-Breast04 trial (NCT03734029) demonstrated significantly improved progression-free survival (PFS) and overall survival (OS) in pts with HER2-low mBC treated with T-DXd vs TPC. Consistent efficacy was also demonstrated in pts with BMs at baseline with T-DXd vs TPC. In this exploratory analysis, we provide additional intracranial (IC) efficacy data in pts with BMs at baseline.

Methods

Pts with centrally confirmed HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization−) mBC who were previously treated with 1 or 2 lines of chemotherapy were randomized (2:1) to T-DXd or TPC. Pts with investigator-assessed clinically stable and treated BMs at baseline were eligible, and exploratory analyses of IC clinical activity were completed. Analysis was based on central review of brain MRI or CT scans. Endpoints included IC objective response rate (ORR) by blinded independent central review (BICR), best overall response, clinical benefit rate, disease control rate, and IC PFS by BICR.

Results

Of 35 pts with BICR-assessed BMs at baseline, 24 pts received T-DXd and 11 received TPC. Like the full dataset, most pts with BMs at baseline had hormone receptor-positive tumors (T-DXd, 75.0%; TPC, 72.7%). Of those pts who received ≥1 dose of trial drug, median treatment duration was 6.6 mo (mo; range, 0.3-24.3 mo) for T-DXd (n = 24) and 1.4 mo (range, 0.4-17.4 mo) for TPC (n = 9); 20.8% and 11.1% of these pts remained on T-DXd and TPC for >12 mo, respectively. IC response data are shown in the table. Median IC PFS by BICR for T-DXd was 9.7 mo (95% CI, 4.4-15.1 mo) vs not evaluable for TPC, due to small pt numbers.

Conclusions

In this exploratory analysis, IC responses favored T-DXd over TPC in pts with clinically stable and treated baseline BMs. While only a small number of pts were included here, the IC efficacy data suggest a clinical benefit of T-DXd over TPC. Table: 388P

Summary of intracranial responses

Clinical trial identification

NCT03734029.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Lauren Carroll, MS, MPH, Toinette Labuschagne, MS, and Katie Henderson, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

This study was funded by Daiichi Sankyo, Inc., and AstraZeneca.

Disclosure

J. Tsurutani: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Eisai, Eli Lilly, Ono. T. Yamashita: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Pfizer, Daiichi Sankyo, Astraseneca, Taiho, Novartis Pharma, Nippon Kayaku, Eli Lilly, Kyowa kirin. F. Riaz: Financial Interests, Institutional, Funding, Site PI for Industry Sponsored Trial: Genentech Roche, Greenwich Sciences, AstraZeneca, Daiichi Sankyo, Novartis. R. Yerushalmi: Financial Interests, Personal, Advisory Board, invited Speaker, Research Grant,: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board, Invited Speaker: Novartis, MSD, AstraZeneca, Eli Lilly, Gilead; Financial Interests, Personal, Invited Speaker: Teva, Medison; Financial Interests, Personal, Advisory Board, Research Grant: Rhenium-Oncotest; Financial Interests, Personal, Funding, (Research Grant): Exact Science. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Local PI, Clinical Trial Budget: AstraZeneca, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Coordinating PI, Clinical Trial Budget: Eisai; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. N. Niikura: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Daiichi Sankyo, Chugai, Eli Lilly, MSD; Financial Interests, Personal and Institutional, Research Grant: Chugai, Eisai, Nippon Kayaku; Financial Interests, Personal and Institutional, Coordinating PI: Daiichi Sankyo. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp & Dohme, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardant Health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. H. Simon: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Viatris, AstraZeneca; Financial Interests, Personal, Invited Speaker, Travel/accomodation: Novartis, Lilly; Financial Interests, Personal, Other, Travel/accomodation: Eisai, Gilead, Pfizer; Financial Interests, Personal, Advisory Role: Roche. C. Orbegoso Aguilar, K. Tecson, L. Yung: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. S. Modi: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Genentech, AstraZeneca, Seagen, Macrogenics; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Steering Committee Member: daiichi sankyo; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Genentech, AstraZeneca, Seagen. All other authors have declared no conflicts of interest.