Background

T-DXd showed superior progression-free survival (PFS) vs T-DM1 (HR, 0.28; 95% CI, 0.22-0.37), with manageable safety, in pts with HER2+ MBC in DESTINY-Breast03 (NCT03529110; Cortes 2022). We present additional patient subgroups by disease history and prior treatment.

Methods

Pts with HER2+ MBC whose disease had progressed on or after trastuzumab and a taxane were randomized 1:1 to receive T-DXd or T-DM1. An exploratory analysis was conducted of subgroups based on presence of de novo (stage IV disease at initial diagnosis) or recurrent (diagnosed at early stage, developed metastatic disease later) MBC, early progression (disease progression within 6 months [mo] after [neo]adjuvant therapy [12 mo for pertuzumab-containing regimens]), and number and type of prior treatments.

Results

PFS (by BICR, data cutoff May 21, 2021) benefit was observed with T-DXd vs T-DM1 for both pts with de novo (HR, 0.35) and recurrent (HR, 0.28) MBC (table). Confirmed objective response rates were consistent between de novo (T-DXd, 79.6% [95% CI, 69.9-87.2] vs T-DM1, 33.7% [24.7-43.6]) and recurrent (T-DXd, 79.8% [72.9-85.6] vs T-DM1, 34.6% [27.2-42.5]) MBC. Within the subgroup of pts with recurrent MBC, there were 35 early progressors (T-DXd, n = 15; T-DM1, n = 20); in a sensitivity analysis, PFS (HR, 0.19; 95% CI, 0.05-0.71) was consistent with the primary analysis. PFS benefit for T-DXd vs T-DM1 was observed regardless of the number of prior lines of anti-HER2 therapy (HR, 0.33 for 1 prior line and HR, 0.23 for ≥2 lines). The safety profile of the subgroups was consistent with the primary analysis. Table: 236P

PFS by Disease History, Prior Therapy

Conclusions

In this exploratory analysis, a benefit of T-DXd vs T-DM1 was observed irrespective of disease history and prior treatment, consistent with the results of the overall primary analysis. T-DXd had a manageable safety profile.

Clinical trial identification

NCT03529110.

Editorial acknowledgement

Under the guidance of authors, medical writing and editorial support was provided by Alya R. Raphael, PhD, of ApotheCom and was funded by Daiichi Sankyo.

Legal entity responsible for the study

Daiichi Sankyo and AstraZeneca.

Funding

Daiichi Sankyo and AstraZeneca.

Disclosure

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, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, Astrazeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Invited Speaker, Clinical Trial Budget: AstraZeneca, Eisai, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. H. Iwata: Financial Interests, Personal, Advisory Role, Honoraria: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Personal, Research Grant, Honoraria: Daichi-Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Boehringer Ingelheim, Novartis, Dantari, Lilly, Merck, Puma Biotechnology, Silverback Therapeutics, CytomX, Pfizer, Mersana, Black Diamond, H3 Biomedicine, Daiichi Sankyo, AstraZeneca, Arvinas, Deciphera Pharmaceuticals, Eisai, Seagen, Arcus, iTeos, Janssen, Loxo, Relay Therapeutics; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Silverback Therapeutics, Millenium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Fochon, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, SeaGen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, Abbvie, Nucana, Orinove, Leap Therapeutics, Zenith Epigenetics, Harpoon, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, Merck, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses, Incyte, Jacobio, Mabspace Biosciences, Myraid Genetic Labs, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Vincerx Pharma. S.A. Hurvitz: Financial Interests, Institutional, Research Grant: Ambrx, Amgen, AstraZeneca, Bayer, Cytomx, Daiichi Sankyo, Dignitana, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Orinove, Pieris, PUMA, Radius, Sanofi, Seattle Genetics/Seagen, Zymeworks, Phoenix Molecular Designs, Ltd, Ambrx, Samumed; Financial Interests, Institutional, Advisory Role: Novartis, Lilly, AstraZeneca, Daiichi Sankyo, GNE/Roche, Sanofi; Financial Interests, Institutional, Principal Investigator: Novartis, Daiichi Sankyo, SeaGen, GNE/Roche; Non-Financial Interests, Other, Travel Expenses: Lilly; Non-Financial Interests, Advisory Role: 4DPharma, Ambrx, Amgen, Artios, Arvinas, Daiichi Sankyo, Genentech/Roche, Immunomedics, Macrogenics, Eli Lilly, Novartis, NK Max, Pieris, Pyxis, Seagen, Biotheranostics. A. Egorov, J. Cathcart, Y. Liu, E. Bako: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences; Financial Interests, Personal, Advisory Board, Advisory Board: Exact Science, Celcuity; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA.