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DESTINY-Breast09

Phase III Study of Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive, First-line Metastatic Breast Cancer (DESTINY-Breast09)

Phase 3N = 1,157NCT04784715

Population
HER2-positive advanced or metastatic breast cancer with no previous chemotherapy or HER2-directed therapy for metastatic disease
Design
Phase 3 randomised trial, 1:1:1 allocation to trastuzumab deruxtecan plus pertuzumab, trastuzumab deruxtecan plus placebo, or a taxane with trastuzumab and pertuzumab (THP). The first report is a prespecified interim analysis of the T-DXd plus pertuzumab and THP arms; the T-DXd plus placebo arm remains blinded until the final PFS analysis.
Primary endpoint
PFS
Arms
  • Taxane, trastuzumab and pertuzumab (THP) (control, n = 387): Taxane plus trastuzumab plus pertuzumab
  • Trastuzumab deruxtecan plus pertuzumab (experimental, n = 383): Trastuzumab deruxtecan plus pertuzumab
  • Trastuzumab deruxtecan plus placebo (experimental): Trastuzumab deruxtecan plus placebo (data blinded in the first report)
People
Tolaney SM
PFSHR 0.56 (95% CI 0.44–0.71)Δ median PFS+13.8 monthsΔ ORR+6.5 pointsΔ median DOR+12.8 months
Show the numbers
Results reported for DESTINY-Breast09
EndpointAnalysisTrastuzumab deruxtecan plus pertuzumab / Trastuzumab deruxtecan plus placeboTaxane, trastuzumab and pertuzumab (THP)Effect
PFSPatients in the T-DXd plus pertuzumab (383) and THP (387) groups at the interim analysis (analysis population not stated in the abstract)PFS by blinded independent central reviewinterimTolaney 2026median 40.7 monthsmedian 26.9 monthsHR 0.56 (95% CI 0.44–0.71)P<0.00001Prespecified interim analysis (data cutoff 26 February 2025); the P-value boundary for superiority was 0.00043. The per-group patient numbers 383 and 387 are as given in the abstract, which does not say whether they are randomised or analysed numbers.
ORRPatients in the T-DXd plus pertuzumab (383) and THP (387) groups at the interim analysis (analysis population not stated in the abstract)interimTolaney 202685.1%78.6%Confirmed response; complete responses in 15.1% with trastuzumab deruxtecan plus pertuzumab and 8.5% with THP.
DORPatients in the T-DXd plus pertuzumab (383) and THP (387) groups at the interim analysis (analysis population not stated in the abstract)interimTolaney 2026median 39.2 monthsmedian 26.4 months—
Results reported for DESTINY-Breast09
EndpointAnalysisTrastuzumab deruxtecan plus pertuzumab / Trastuzumab deruxtecan plus placeboTaxane, trastuzumab and pertuzumab (THP)Effect
PFSPatients in the T-DXd plus pertuzumab (383) and THP (387) groups at the interim analysis (analysis population not stated in the abstract)PFS by blinded independent central reviewinterimTolaney 2026median 40.7 monthsmedian 26.9 monthsHR 0.56 (95% CI 0.44–0.71)P<0.00001Prespecified interim analysis (data cutoff 26 February 2025); the P-value boundary for superiority was 0.00043. The per-group patient numbers 383 and 387 are as given in the abstract, which does not say whether they are randomised or analysed numbers.
ORRPatients in the T-DXd plus pertuzumab (383) and THP (387) groups at the interim analysis (analysis population not stated in the abstract)interimTolaney 202685.1%78.6%Confirmed response; complete responses in 15.1% with trastuzumab deruxtecan plus pertuzumab and 8.5% with THP.
DORPatients in the T-DXd plus pertuzumab (383) and THP (387) groups at the interim analysis (analysis population not stated in the abstract)interimTolaney 2026median 39.2 monthsmedian 26.4 months—
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.560.44–0.71
Illustrative — modelled from reported values, not trial data. PFS, interim.
0%25%50%75%100%020406080100Months (modelled)
  • Taxane, trastuzumab and pertuzumab (THP) (control)
  • Trastuzumab deruxtecan plus pertuzumab (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsTaxane, trastuzumab and pertuzumab (THP)Trastuzumab deruxtecan plus pertuzumab
0100.0%100.0%
2552.5%65.3%
5126.9%42.0%
7614.1%27.4%
1027.2%17.6%
Illustrative — modelled from reported values, not trial data. DOR, interim.
0%25%50%75%100%020406080Months (modelled)
  • Taxane, trastuzumab and pertuzumab (THP) (control)
  • Trastuzumab deruxtecan plus pertuzumab (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsTaxane, trastuzumab and pertuzumab (THP)Trastuzumab deruxtecan plus pertuzumab
0100.0%100.0%
2551.9%64.3%
4927.6%42.0%
7414.3%27.0%
987.6%17.7%
Primary publication: Tolaney SM, Jiang Z, Zhang Q, Barroso-Sousa R, Park YH, Rimawi MF, et al. Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2026;394(6):551-562. PubMedDOI

Appears in

Sources

  1. Tolaney SM, Jiang Z, Zhang Q, Barroso-Sousa R, Park YH, Rimawi MF, et al. Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2026;394(6):551-562.

    PubMedDOI