Abstract 186P
Background
T-DXd is approved as 2L+ treatment for pts with HER2+ or HER2-low (IHC 1+/IHC 2+/ISH−) mBC based on efficacy in DESTINY-Breast (DB)-01/02/03/04 trials. There are no published pooled safety data for T-DXd in pts with mBC.
Methods
Analysis included pts with HER2+ (DB-01/02/03) or HER2-low (DB-04) mBC. DB-01 was a single-arm study of T-DXd after trastuzumab emtansine (T-DM1). DB-02 compared T-DXd to treatment of physician’s choice (TPC) after T-DM1. DB-03 compared T-DXd to T-DM1 after trastuzumab (± pertuzumab) + taxane. DB-04 compared T-DXd to TPC after 1 or 2 chemotherapy lines.
Results
Drug-related treatment-emergent adverse event (TEAE) rates for T-DXd were similar in DB-01/02/03/04 (Table). Median time (range) to T-DXd discontinuation due to any TEAE in DB-01/02/03/04 was 187.0 (8-783), 248.5 (2-759), 337.0 (104-1163), and 149.0 (3-740) d, respectively. Pooled T-DXd (N = 1216) adjudicated drug-related interstitial lung disease (ILD) rate was 12.7%; most grade 1 or 2 (11%); median (range) time to onset 176 (26-960) d; median (range) duration 56.5 (1-542) d. Rates of any-grade adjudicated drug-related ILD with T-DXd after <3/≥3 prior therapy lines were 14.3%/15.9% in DB-01, 7.1%/11.3% in DB-02, 17.9%/13.1% in DB-03, and 5.7%/13.2% in DB-04. Median treatment duration was ∼2-fold longer for pooled T-DXd (13.9 months; range, 0.2-45.1) vs comparators. Exposure-adjusted incidence rates of grade ≥3 TEAEs were 0.48 (T-DXd), 0.77 (TPC, DB-02), 0.65 (T-DM1), and 1.81 (TPC, DB-04) pt-years. Higher rates of drug-related nausea (72.4% vs 30.8%, 27.6%, 23.8%), vomiting (37.3% vs 11.8%, 5.7%, 9.9%), and fatigue (51.2% vs 31.3%, 29.1%, 42.4%) occurred with T-DXd vs TPC (DB-02), T-DM1 (DB-03), and TPC (DB-04). Table: 186P
| Drug-related TEAEs with T-DXd treatment, n (%) | DB-01 N=184 | DB-02 N=404 | DB-03 N=257 | DB-04 N=371 |
| Reported in ≥40% of pts | 183 (99.5) | 394 (97.5) | 252 (98.1) | 357 (96.2) |
| Nausea | 142 (77.2) | 277 (68.6) | 190 (73.9) | 271 (73.0) |
| Fatigue | 110 (59.8) | 209 (51.7) | 123 (47.9) | 181 (48.8) |
| Alopecia | 86 (46.7) | 142 (35.1) | 100 (38.9) | 141 (38.0) |
| Vomiting | 81 (44.0) | 131 (32.4) | 115 (44.7) | 127 (34.2) |
| Neutropenia | 63 (34.2) | 134 (33.2) | 115 (44.7) | 125 (33.7) |
| Serious | 27 (14.7) | 46 (11.4) | 33 (12.8) | 49 (13.2) |
| Associated with discontinuation | 33 (17.9) | 58 (14.4) | 51 (19.8) | 57 (15.4) |
| Associated with dose reduction | 43 (23.4) | 95 (23.5) | 65 (25.3) | 83 (22.4) |
| Associated with death | 3 (1.6) | 4 (1.0) | 0 | 7 (1.9) |
Conclusions
The safety profile of T-DXd was consistent in pts with HER2+ and HER2-low mBC across DB-01/02/03/04. Except in DB-03, ILD rates with T-DXd were similar or higher after ≥3 prior therapy lines.
Clinical trial identification
NCT03248492, NCT03523585, NCT03529110, NCT03734029.
Editorial acknowledgement
Under the guidance of authors, assistance in medical writing and editorial support was provided by Kim Enfield, PhD, and Sara Duggan, PhD, of ApotheCom.
Legal entity responsible for the study
Daiichi Sankyo, Inc., and AstraZeneca.
Funding
This study was funded by Daiichi Sankyo, Inc., and AstraZeneca. Medical writing support (ApotheCom) was funded by Daiichi Sankyo, Inc.
Disclosure
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, Daiichi Sankyo; Financial Interests, Institutional, Other, Research Grant: AstraZeneca, Pfizer, Roche, MSD; Financial Interests, Institutional, Invited Speaker: Pfizer; Non-Financial Interests, Principal Investigator: AstraZeneca, Pfizer, Novartis, MSD, Lilly, Roche, Daiichi Sankyo. W. Jacot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Novartis, Roche, Pfizer, Eli Lilly, MSD, BMS, Chugai, Seagen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory Board: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Invited Speaker: Roche, Roche, Novartis, Daiichi Sankyo, Daiichi Sankyo. 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, Peer Voice, Curio, Reach MD/MedIQ, Imedex, MD Outlook, Prime Oncology, Reach MD, OncLive; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Personal, Royalties, author medical book: McGraw; Financial Interests, Personal, Royalties: Elsevier, Springer, Sage, Wolters Kluwer, Wiley; Financial Interests, Institutional, Invited Speaker: Ambrx, AstraZeneca, Arvinas, Daiichi Sankyo, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Pieris, PUMA, Radius, sanofi, Seattle Genetics, Dignitana, Zymeworks, Phoenix Molecular Designs, Ltd., Celcuity, cytomx, Dantari, G1 Therapeutics, Greenwich Life Sciences, Loxo Oncology, orinove, Orum; Financial Interests, Institutional, Research Grant: Ambrx; Financial Interests, Invited Speaker: Greenwich Life Sciences, Orum; Non-Financial Interests, Advisory Role: Daiichi Sankyo, Novartis, Ambrx, 4DPharma, Dantari, Macrogenics, Lilly, Artios, Roche, Pyxis, Amgen, Pieris, Arvinas, Immunomedics/Gilead, Briacell, Jazz Pharmaceuticals, Boehringer Ingelheim, Stemline/Menarini; Non-Financial Interests, Principal Investigator: Daiichi Sankyo, Genentech, Seattle Genetics; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Other, speaker: National Breast Cancer Coalition; Non-Financial Interests, Member, site representative for breast cancer guidelines: National Comprehensive Cancer Network. S. Modi: Financial Interests, Personal, Advisory Board, And Invited Speaker: Genentech, Daiichi Sankyo, AstraZeneca, Seagen, Gilead; Financial Interests, Institutional, Sponsor/Funding: Genentech, Daiichi Sankyo, AstraZeneca, Seagen, DualityBio, Nuvation; Financial Interests, Personal, Advisory Board: DualityBio. T. Yamashita: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Daiichi Sankyo, Eli Lilly, Novartis Pharma, Taiho, Nippon Kayaku, AstraZeneca, Kyowa kirin, Pfizer; Financial Interests, Institutional, Research Grant: Chugai, Taiho, Nippon Kayaku; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo, Eli Lilly, Pfizer, AstraZeneca, Seagen, MSD, Kyowa kirin. B. Xu: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca. E. Tokunaga: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Daiichi Sankyo. K.S. Lee: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, MSD, Eisai, Lilly, Roche, Bixink. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Sanofi; Financial Interests, Personal, Invited Speaker: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Pfizer, Sanofi, Taiho; Financial Interests, Personal and Institutional, Invited Speaker: Chugai, Daiichi Sankyo, AstraZeneca, MSD, Amgen, Sanofi, Lilly, Novartis, Bayer, Pfizer, Kyowa Hakko Kirin, Behringer, Nihon Kayaku. 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; Financial Interests, Personal, Officer, I am CSO in this non-profit: Translational Breast Cancer Research COnsortium; Financial Interests, Personal, Stocks/Shares, Spouse: PureTech; Financial Interests, Institutional, Invited Speaker: Pfizer, Macrogenics, Genentech, Roche. F. André: Financial Interests, Personal, Advisory Board: Lilly FRANCE; Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, Owkin, Novartis, Guardant Health, N-Power Medicine, Servier, Gilead, Boston Pharmaceutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi, Guardant Health, Owkin. N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Seagen, Art Tempi, Onkowissen, Medscape, Gilead, Sanofi, Zuelligpharma, Viatris; Financial Interests, Personal, Other, IDMC: Roche; Financial Interests, Personal, Advisory Board: Sandoz-Hexal, Seagen, Aptitude Health, Pfizer, Gilead, Sanofi; Financial Interests, Personal, Other, Husband: WSG (Husband); Financial Interests, Personal, Ownership Interest: West German Study Group; Financial Interests, Institutional, Funding: AstraZeneca, BMS, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Palleos, Seagen, TRIO, WSG; Non-Financial Interests, Member, Member German AGO Breast Guideline Committee: AGO Breast Committee; Non-Financial Interests, Member, Breast Cancer Educational Programs: ESO/ESCO; Other, Founding Editor: BreastCare Journal. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: NAPO, Mylan/Viatris, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly, Pfizer, OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Daiichi, AstraZeneca, Gilead Sciences, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. E. Mathias, M. Karnoub, S. Ashfaque, Y. Cheng: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. W.T. Pasteiner: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Austria GmbH. S. Kim: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Lilly, DaeHwa Pharma, ISU Abx, Daiichi Sankyo, BeiGene, Samsung Bioepics, OBI pharma; Financial Interests, Personal, Invited Speaker: Legochem Bioscience; Financial Interests, Personal, Ownership Interest: Genopeaks; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Genzyme, DongKook Pharm Co. All other authors have declared no conflicts of interest.