377O - A pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) with brain metastases (BMs) from DESTINY-Breast (DB) -01, -02, and -03

Background

T-DXd is approved for treatment of pts with HER2+ unresectable or mBC who have received ≥1 prior anti-HER2-based regimens. We report exploratory pooled efficacy and safety data of T-DXd vs comparator (comp) in pts from DB-01, DB-02, and DB-03 with treated/stable (treated) and untreated/active (untreated; from DB-02/-03) BMs at baseline, as defined by the US FDA (FDA 2020).

Methods

DB-01/-02 enrolled pts who were resistant/refractory to trastuzumab emtansine (T-DM1); DB-03 included pts previously treated with trastuzumab and taxane. T-DXd data and ad hoc exploratory intracranial analyses were pooled from DB-01/-02/-03. Comp data, physician’s choice chemotherapy and T-DM1, were pooled from DB-02 and -03, respectively. Endpoints were intracranial (IC) objective response rate (ORR; complete [CR] or partial response [PR] in brain) per blinded independent central review (BICR) by RECIST, IC duration of response (DoR), central nervous system-progression-free survival (CNS-PFS) by BICR, and safety.

Results

Of the 148 pts with BMs at baseline who received T-DXd, 104 (70.3%) had treated and 44 (29.7%) had untreated BMs. Pts had a median of 3 (range, 1.0-14.0) prior regimens in the metastatic setting. Median treatment duration was 12.7 mo (range, 0.7-45.1) with T-DXd and 5.6 mo (range, 0.1-43.0) with comp. Efficacy data are in the Table. Any-grade drug-related treatment-emergent adverse events (TEAEs), drug-related grade ≥3 TEAEs, and serious drug-related AEs were observed in 94.5%, 43.2%, and 13.0% of pts with T-DXd, vs 94.0%, 36.1%, and 7.2% with comp, respectively.

Conclusions

T-DXd exhibited robust IC responses in pts with treated and, notably, untreated BMs vs comp. Although pt numbers were small and not statistically tested, numerically longer median IC-DoR and CNS-PFS were observed in pts with untreated BMs with T-DXd. Safety was acceptable and generally manageable with T-DXd. Table: 377O

IC efficacy summary

NE, not evaluable.

Clinical trial identification

NCT03248492; NCT03523585; NCT03529110.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Andre Wang, PharmD, and Laura Halvorson, 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

S.A. Hurvitz: Financial Interests, Personal, Invited Speaker: Clinical Care Options, axis medical, cancer expert now, ICHE, MJH Associates, PER, Primo, Projects in Knowledge, Prova Education, Research to Practice, Ultimate Medical Academy, Vaniam, WebMD, Peer Education, PrecisCA; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Personal, Ownership Interest, spouse: Ideal Implant; Financial Interests, Personal, Royalties, author medical book: McGraw; Financial Interests, Personal, Royalties: Elsevier, Springer, Sage, Wolters Kluwer, Wiley; Financial Interests, Institutional, Local PI: Ambrx, AstraZeneca, Arvinas, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Pieris, PUMA, Radius, sanofi, Seattle Genetics, Dignitana, Zymeworks, Phoenix Molecular Designs, Ltd, cytomx, Dantari, G1 Therapeutics, Greenwich Life Sciences, Loxo Oncology, Orinove, Orum; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, Celcuity; Financial Interests, Institutional, Research Grant: Samumed, Ambrx; Financial Interests, Steering Committee Member: Greenwich Life Sciences, Orum; Financial Interests, Principal Investigator: Genentech, Daiichi Sankyo, Seattle Genetics; Financial Interests, Advisory Role: Daiichi Sankyo, Novartis, Ambrx, 4DPharma, Dantari, Macrogenics, Lilly, Artios, Roche, Pyxis, Amgen, Pieris, Arvinas, Immunomedics/Gilead; Financial Interests, Member: ASCO, AACR; Financial Interests, Other, speaker: National Breast Cancer Coalition; Financial Interests, Member, site representative for breast cancer guidelines: National Comprehensive Cancer Network. 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. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche, Novartis, MSD; Financial Interests, Institutional, Other, Research Grant: AstraZeneca, Pfizer, Roche, MSD; Financial Interests, Principal Investigator: AstraZeneca, Pfizer, Novartis, MSD, Lilly, Roche, Daiichi Sankyo. W. Chung: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Viatris; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, MSD, Novartis, Pfizer. S. Kim: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Lilly, DaeHwa Pharma, ISU Abx, Daiich-Sankyo, Beigene, HLB Life Science, Samsung Bioepics, OBI pharma; Financial Interests, Personal, Invited Speaker: Legochem Bioscience; Financial Interests, Personal, Ownership Interest: Genopeaks, Neogene TC; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Genzyme, DongKook Pharm Co. 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. T. Yamashita: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, Taiho, Kyowa Kirin, Novartis Pharma, Nippon Kayaku, Eli Lilly . J. Pedrini: Financial Interests, Institutional, Principal Investigator: AstraZeneca, Roche, Daiichi Sankyo, Sanofi, PPD, Seagen, MSD. 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. Harbeck: Financial Interests, Personal and Institutional, Other, Honoraria for lectures and/or consulting; Clinical Trials: Amgen, AstraZeneca, Daiichi Sankyo, EPG Communication, Gilead, Eli Lilly, MEDSCAPE, MSD, Novartis, Pierre-Fabre, Roche, Sandoz, Sanofi, Seagen, Springer, Viatris, Zuelligpharma. I. Krop: Financial Interests, Personal, Advisory Board: Genentech/Roche, AstraZeneca, Daiichi Sankyo, Macrogenics, Seagen; Financial Interests, Personal, Other, DSMB member: Novartis; Financial Interests, Personal, Other, DSMC member: Merck; Financial Interests, Personal, Full or part-time Employment, Spouse: PureTech, Freeline; Financial Interests, Personal, Stocks/Shares, Spouse: PureTech, Freeline; Financial Interests, Institutional, Coordinating PI: Pfizer, Macrogenics, Genentech/Roche. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Other, Advisory Board: Ellipsis; 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, Coordinating PI, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; 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, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO. E. Mathias, J. Cathcart, A. Cagnazzo, S. Ashfaque : Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. A. Egorov: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Financial Interests, Institutional, Other, advisory board: Guardant Health; Financial Interests, Institutional, Other, Advisory board: Medimmune, Gilead, Relay therapeutics; Other, Founder: Pegacsy. All other authors have declared no conflicts of interest.