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DESTINY-Breast09

Showed Enhertu plus pertuzumab beats the decade-old first-line standard for HER2-positive metastatic breast cancer.

PFS 40.7 vs 26.9 months (HR 0.56). Replaces CLEOPATRA-era THP as first-line.

Setting
First-line HER2+ metastatic breast cancer: T-DXd + pertuzumab vs THP
Phase
Phase 3
Sponsor
Daiichi Sankyo / AstraZeneca
Registry
Headline result
PFS HR 0.56.
Reported
2025
Enrolled
1157
Replication
Single pivotal trial versus the CLEOPATRA-era standard; the T-DXd monotherapy arm is still blinded. Consistent with the class's performance in DESTINY-Breast03.

Outcomes

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In plain words
What these results mean for people, not percentages
1,157 people took part
Progression-free survival (BICR), T-DXd + pertuzumab vs THPprimarysurrogate endpoint
  • Median 40.7 vs 26.9 months with Trastuzumab deruxtecan + pertuzumab compared with Taxane + trastuzumab + pertuzumab; about 13.8 months longer for half the group.
  • A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
  • Put another way, the treated group had about 44 percent lower chance of the event at any given time (hazard ratio 0.56, likely range 0.44 to 0.71).
  • This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
Objective response rateresponse endpoint
  • 85.1 vs 78.6 out of 100 had their tumour shrink with Trastuzumab deruxtecan + pertuzumab compared with Taxane + trastuzumab + pertuzumab; 6.5 more per 100.
  • Roughly one extra person helped for every 15 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
  • A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
Overall survivalsurvival endpoint
  • Numbers are not recorded here for this endpoint. Trastuzumab deruxtecan + pertuzumab: Immature at the interim analysis; early trend favoured T-DXd + pertuzumab.; Taxane + trastuzumab + pertuzumab.
  • Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
  • Immature at the interim analysis; early trend favoured T-DXd + pertuzumab.
Be careful
  • These results apply to the people the trial enrolled: First-line HER2+ metastatic breast cancer: T-DXd + pertuzumab vs THP. People in a different situation may not see the same effect.
  • The trial selected people by a biomarker (HER2); the result should not be assumed for people whose cancer does not have it.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

1,157 participants enrolled.

Progression-free survival (BICR), T-DXd + pertuzumab vs THPprimary
HR 0.56 (0.44–0.71) · p <0.00001
Trastuzumab deruxtecan + pertuzumab
40.7 mo
Taxane + trastuzumab + pertuzumab
26.9 mo
Source
Objective response rate
Trastuzumab deruxtecan + pertuzumab85.1 of 100
Taxane + trastuzumab + pertuzumab78.6 of 100
Overall survival

Immature at the interim analysis; early trend favoured T-DXd + pertuzumab.

EndpointArmnValueHR (95% CI)pSource
Progression-free survival (BICR), T-DXd + pertuzumab vs THPprimaryTrastuzumab deruxtecan + pertuzumab38340.7 months0.56 (0.44–0.71)<0.00001link
Taxane + trastuzumab + pertuzumab38726.9 months
Objective response rateTrastuzumab deruxtecan + pertuzumab85.1%
Taxane + trastuzumab + pertuzumab78.6%
Overall survivalTrastuzumab deruxtecan + pertuzumabImmature at the interim analysis; early trend favoured T-DXd + pertuzumab.
Taxane + trastuzumab + pertuzumab
Replication
Single pivotal trial versus the CLEOPATRA-era standard; the T-DXd monotherapy arm is still blinded. Consistent with the class's performance in DESTINY-Breast03.

Connected

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