Background
DB-02 (NCT03523585) is a randomized, open-label, phase III trial of T-DXd vs TPC in pts previously treated with T-DM1 for HER2+ mBC. At primary study analysis (data cutoff [DCO], Jun 30, 2022), T-DXd showed statistically significant improvement in progression-free survival (PFS) and OS vs TPC. We report updated efficacy and safety results (DCO, Sep 29, 2023), including OS.
Methods
Pts with HER2+ mBC were randomly assigned 2:1 to T-DXd or TPC (trastuzumab + capecitabine [cap] or lapatinib + cap). This analysis includes OS, PFS, PFS from time of randomization to the progression on next line of therapy or death (PFS2) by investigator, and safety.
Results
608 pts were randomized (T-DXd, n = 406; TPC, n = 202). At DCO, median (range) follow-up (F/U) was 30.2 mo (0.8-60.7) with T-DXd and 20.5 mo (0.0-60.6) with TPC. In the T-DXd and TPC arms, 86.4% and 100% of pts discontinued treatment, respectively; primary reason was progressive disease (47.8%, 73.8%). Median (95% CI) OS was 35.7 mo (30.9-40.8) with T-DXd vs 25.0 mo (20.4-31.5) with TPC. Median PFS2 was 33.0 mo (T-DXd) vs 15.0 mo (TPC). Additional results are in the table. T-DXd was received as poststudy anticancer treatment by 12.9% of pts (32/248) in the T-DXd arm and by 46.6% (69/148) in the TPC arm. Treatment-emergent adverse events (TEAEs) associated with discontinuation occurred in 21.5% of pts with T-DXd and 9.7% with TPC. There were 46 (11.4%) adjudicated drug-related interstitial lung disease/pneumonitis cases with T-DXd; 4 since primary DCO (2 grade 1; 2 grade 2). Table: 182MO
Updated efficacy and safety
| T-DXd n = 406 | TPC n = 202 | |
| mPFSa (95% CI), mo | 16.7 (14.7-19.6) | 5.5 (4.4-6.8) |
| HR (95% CI) | 0.30 (0.24-0.37) | |
| mPFS2a (95% CI), mo | 33.0 (28.6-36.6) | 15.0 (13.0-18.1) |
| HR (95% CI) | 0.42 (0.33-0.53) | |
| mOS (95% CI), mo | 35.7 (30.9-40.8) | 25.0 (20.4-31.5) |
| HR (95% CI) | 0.69 (0.55-0.86) | |
| Pts with events, n (%) | 211 (52.0) | 119 (58.9) |
| 24-mo OS rate, % (95% CI) | 64.6 (59.6-69.2) | 51.9 (44.4-58.9) |
| 36-mo OS rate, % (95% CI) | 49.2 (44.0-54.3) | 36.6 (29.5-43.8) |
| T-DXd n = 404 | TPC n = 195 | |
| mTreatment duration, mo (range) | 11.3 (0.7-60.7) | ∼4.5 (0.1-50.6) |
| Any-grade TEAEs, n (%) | 403 (99.8) | 185 (94.9) |
| Grade ≥3 TEAEs, n (%) | 224 (55.4) | 87 (44.6) |
| Serious TEAEs, n (%) | 114 (28.2) | 46 (23.6) |
m, median; aBy investigator assessment.
Conclusions
Results reinforce the substantial benefit of T-DXd over TPC in pts with HER2+ mBC previously treated with T-DM1, demonstrated by clinically meaningful improvement in OS, PFS, and PFS2. The safety profile of T-DXd continues to be manageable, with no long-term toxicity observed with longer F/U.
Clinical trial identification
NCT03523585.
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. Medical writing support (ApotheCom) 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. 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. 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. T. Takano: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Chugai, Eli Lilly. T.N. Fehm: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Novartis, Roche, AstraZeneca, MSD, Eisai. 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. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Merck, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. K. Yonemori: Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR pharma, MSD, Boehringer Ingelheim, Ono, Daiichi Sankyo, Bayer, Sanofi, Janssen; Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gilead, OncXerna, Takeda, Novartis, MSD, Henlius; Financial Interests, Institutional, Research Grant: MSD, Daiichi Sankyo, Merck Biopharma, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe; Financial Interests, Personal, Principal Investigator: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Merck Biopharma, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe. A. Prat: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Pfizer, Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, Guardant Health, Peptomyc, Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis, Roche, Nanostring, Sysmex, Medsir, Pfizer; Financial Interests, Personal, Stocks/Shares: Pangea; Financial Interests, Personal, Ownership Interest: Reveal genmics. S. Nakatani: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Ltd.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Ltd. S. Ashfaque: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. W. Lu: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. A. Egorov: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Ltd.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Oncology. 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. All other authors have declared no conflicts of interest.
