DESTINY-Breast04
A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects
Phase 3N = 557NCT03734029
- Population
- HER2-low metastatic breast cancer after one or two previous lines of chemotherapy (88.7% hormone receptor-positive)
- Design
- Phase 3 randomised trial, 2:1 allocation to trastuzumab deruxtecan or the physician's choice of chemotherapy. HER2-low was defined as IHC 1+ or IHC 2+ with a negative in situ hybridisation result. The primary endpoint was PFS in the hormone receptor-positive cohort.
- Primary endpoint
- PFS
- Arms
- Physician's choice of chemotherapy (control, n = 184): Chemotherapy chosen by the physician
- Trastuzumab deruxtecan (experimental, n = 373): Trastuzumab deruxtecan
- People
- Modi S
PFSHR 0.51Δ median PFS+4.7 monthsOSHR 0.64Δ median OS+6.4 monthsPFSHR 0.5Δ median PFS+4.8 months
Show the numbers
| Endpoint | Analysis | Trastuzumab deruxtecan | Physician's choice of chemotherapy | Effect |
|---|---|---|---|---|
| PFSHormone receptor-positive cohort (494 patients) | primaryModi 2022 | median 10.1 months | median 5.4 months | HR 0.51P<0.001Primary endpoint. No confidence interval is given in the abstract. |
| OSHormone receptor-positive cohort (494 patients) | primaryModi 2022 | median 23.9 months | median 17.5 months | HR 0.64P=0.003Key secondary endpoint, reported with the primary analysis. No confidence interval is given in the abstract. |
| PFS | primaryModi 2022 | median 9.9 months | median 5.1 months | HR 0.5P<0.001Key secondary endpoint; all randomised patients. No confidence interval is given in the abstract. |
| OS | primaryModi 2022 | median 23.4 months | median 16.8 months | HR 0.64P=0.001Key secondary endpoint; all randomised patients. No confidence interval is given in the abstract. |
| OSOverall cohort (all randomised patients) | long term-updatemedian follow-up 32 monthsModi 2025 | median 22.9 months | median 16.8 months | HR 0.69 (95% CI 0.55–0.86)Long-term survival analysis. In the hormone receptor-positive cohort median OS was 23.9 vs 17.6 months (HR 0.69; 95% CI 0.55 to 0.87). |
| Endpoint | Analysis | Trastuzumab deruxtecan | Physician's choice of chemotherapy | Effect |
|---|---|---|---|---|
| PFSHormone receptor-positive cohort (494 patients) | primaryModi 2022 | median 10.1 months | median 5.4 months | HR 0.51P<0.001Primary endpoint. No confidence interval is given in the abstract. |
| OSHormone receptor-positive cohort (494 patients) | primaryModi 2022 | median 23.9 months | median 17.5 months | HR 0.64P=0.003Key secondary endpoint, reported with the primary analysis. No confidence interval is given in the abstract. |
| PFS | primaryModi 2022 | median 9.9 months | median 5.1 months | HR 0.5P<0.001Key secondary endpoint; all randomised patients. No confidence interval is given in the abstract. |
| OS | primaryModi 2022 | median 23.4 months | median 16.8 months | HR 0.64P=0.001Key secondary endpoint; all randomised patients. No confidence interval is given in the abstract. |
| OSOverall cohort (all randomised patients) | long term-updatemedian follow-up 32 monthsModi 2025 | median 22.9 months | median 16.8 months | HR 0.69 (95% CI 0.55–0.86)Long-term survival analysis. In the hormone receptor-positive cohort median OS was 23.9 vs 17.6 months (HR 0.69; 95% CI 0.55 to 0.87). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.69 | 0.55–0.86 |
- Physician's choice of chemotherapy (control)
- Trastuzumab deruxtecan (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Physician's choice of chemotherapy | Trastuzumab deruxtecan |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 46.3% | 66.2% |
| 13 | 18.8% | 41.0% |
| 19 | 8.7% | 27.1% |
| 25 | 4.0% | 18.0% |
- Physician's choice of chemotherapy (control)
- Trastuzumab deruxtecan (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Physician's choice of chemotherapy | Trastuzumab deruxtecan |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 15 | 55.2% | 64.7% |
| 30 | 30.5% | 41.9% |
| 45 | 16.8% | 27.1% |
| 60 | 9.3% | 17.5% |
Appears in
Sources
Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20.
Modi S, Jacot W, Iwata H, Park YH, Vidal Losada M, Li W, et al. Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial. Nat Med. 2025;31(12):4205-4213.