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DESTINY-Breast03 Trial

2L HER2+ metastatic breast cancer (post-trastuzumab + taxane) — Daiichi Sankyo + AstraZeneca

2L HER2+ metastatic breast cancer (post-trastuzumab + taxane)EnhertuESMO 2021 (Cortes et al.) / ASCO 2024 long-term✓ FDA Approved (2022-05)
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Top KOLs Discussing DESTINY-Breast03

Yakup Ergün
Yakup Ergün
@dr_yakupergun
4.7K impressions
Antonio Giordano, MD PhD
Antonio Giordano, MD PhD
@antgiorda
2.3K impressions
Gianmarco Ricagno, MD
Gianmarco Ricagno, MD
@giammi107
258 impressions

DESTINY-Breast03 Key Slides & Visuals

Official trial slides and relevant visuals shared by KOLs at ESMO 2021 (Cortes et al.) / ASCO 2024 long-term. Click any image to expand.

Yakup Ergün
Yakup Ergün @dr_yakupergun
DESTINY-Breast03 Data
4.4K impressions · 69 likes · May 25, 2024
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[Slide 1] T- T- DXd DM1 HR Efficacy (95% CI) n = n = 261 263 52.6 42.7 0.73 mOS (95% (48.7- (35.4- (0.56- CI), mo NE) NE) 0.94) mPFS 29.0 7.2 0.30 (95% CI), (23.7- (6.8- (0.24- mo 40.0) 8.3) 0.38) mPFS2 45.2 23.1 0.53 (95% CI), (39.3- (17.8- (0.41- mo NE) 29.7) 0.68) Confirmed 78.9 36.9 ORR (95% (73.5- (31.0- CI), % 83.7) 43.0) mDoR 30.5 17.0 (95% CI), (23.0- (14.1- mo NE) 23.7) --- [Slide 2] T- T- DXd DM1 Safety, n (%) n = n = 257 261 Any-grade 256 249 TEAEs (99.6) (95.4) Grade 3 149 136 TEAEs (58.0) (52.1) Serious 71 59 TEAEs (27.6) (22.6) --- [Slide 3] (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Updated survival results of DESTINY- Breast03. Abstract Authors Erika P. Hamilton i Sarah Cannon Research Institute, Nashville, TN Erika P. Hamilton, Sara A. Hurvitz, Seock-Ah Im, Hiroji Iwata, Giuseppe Curigliano, Sung-Bae Kim, Joanne Wing- Yan Chiu, Jose Luiz Pedrini, Wei Li, Kan Yonemori, Giampaolo Bianchini, Sherene Loi, Giuliano Santos Borges, Xian Wang, Thomas Bachelot, Shunsuke Nakatani, Shahid Ashfaque, Zhengkang Liang, Anton Egorov, Javier Cortes
Antonio Giordano, MD PhD
DESTINY-Breast03 Data
2.3K impressions · 50 likes · Oct 19, 2025
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[Slide 1] HER2-positive aBC: second-line EMILIA Evolving standards¹⁻³ ~80% reduction in risk of progression or Median No. No. of of Months Events DESTINY-Breast03 death with T-DXd vs. lapatinib + capecitabine Capecitabine 6.4 304 T-DM1 9.6 265 PFS Yes. samply Stratified hazard ratio, 0.65 - 80 Progression-free Surviv 60 (95% CI, 0.55-0.77) Medium months P<0.001 40 PFS probability (%) 60 20 T-DM1 40 Lapatinib-capecitabine 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 20 Months Described TORE No. at Risk 0 T-DAM Lapatinib- 496 404 310 176 129 73 53 35 25 14 9 8 5 1 0 0 0 2 4 6 . to 12 14 16 16 20 22 24 25 30 34 36 38 40 42 44 40 45 52 54 capecitabine Time (months) T-DM1 495 419 341 236 183 130 101 72 54 44 30 18 9 3 1 0 1 Cortes J et al N Engl J Med 2022;386 1143-1154 2 Cortes J et al Nature Med 2024;30 2208-2215 3 Verma S et al H Engl J Med 2012,367:1783-1791 Rupert Bartsch Content of this presentation is copyright and responsibility of the author Permission is required for re-use PFS, progression free survival; ORR, objective response rate BERLIN 2925 ESMO congress

DESTINY-Breast03 Top Tweets

Top tweets by impressions — click to view on X

About the DESTINY-Breast03 Trial

DESTINY-Breast03 established T-DXd as the 2L standard in HER2+ mBC by demonstrating unprecedented PFS and OS improvements over T-DM1. Long-term follow-up confirms durable benefit. T-DXd is now being studied in earlier lines (DESTINY-Breast09) and in HER2-low populations (DESTINY-Breast06).

FDA Approval

FDA APPROVED Enhertu — Adults with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens.

FDA approval date: 2022-05-04.

📄 Source: FDA Press Release →

Trial Methodology & Results

Progression-Free Survival (PFS) — Primary Endpoint (BICR-assessed)

Median: 28.8 months (T-DXd) vs. 6.8 months (T-DM1). HR 0.33 (95% CI 0.26-0.43), P<0.0001 T-DXd produced a >4-fold improvement in median PFS over T-DM1. Confirmed ORR 82.1% with T-DXd.

✓ mPFS 28.8 vs. 6.8 mo (HR 0.33)

📄 Source: KOL commentary on X →

Overall Survival (OS)

Median: 52.6 months (T-DXd, 95% CI 48.7-NE) vs. 42.7 months (T-DM1, 95% CI 35.4-NE). HR 0.73 (95% CI 0.56-0.94) Median OS 52.6 months (95% CI 48.7-NE) with T-DXd vs. 42.7 months (95% CI 35.4-NE) with T-DM1; HR 0.73 (95% CI 0.56-0.94) — 27% reduction in risk of death. Data cutoff Nov 20, 2023; median follow-up 41 months. ~10-month improvement in median OS — the longest OS reported in 2L HER2+ mBC. Published Hamilton et al., Nature Medicine 2024.


📄 Source →

Safety & Tolerability

ILD/pneumonitis (all-grade) 16.7% with T-DXd vs. 3.4% with T-DM1 — requires active monitoring per class labeling. No new Grade ≥3 ILD cases in long-term follow-up. Other TRAEs consistent with established T-DXd profile.

ILD/pneumonitis 16.7% (T-DXd) — active monitoring required

📄 Source →

Clinical Implications

2L standard of care for HER2+ mBC. DESTINY-Breast03 established T-DXd as the 2L standard in HER2+ mBC by demonstrating unprecedented PFS and OS improvements over T-DM1. Long-term follow-up confirms durable benefit. T-DXd is now being studied in earlier lines (DESTINY-Breast09) and in HER2-low populations (DESTINY-Breast06).

DESTINY-Breast03 in the News

Key KOL Sentiments — DESTINY-Breast03