OnCo
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DESTINY-Breast04

Created a new category of breast cancer, HER2-low, by showing Enhertu works in tumours previously called HER2-negative.

OS 23.4 vs 16.8 months (HR 0.64). Standing ovation at ASCO 2022. Roughly half of all breast cancers became eligible for a HER2-directed drug overnight.

Setting
HER2-low metastatic breast cancer after chemotherapy: T-DXd vs chemotherapy
Phase
Phase 3
Sponsor
Daiichi Sankyo / AstraZeneca
Registry
Headline result
OS HR 0.64.
Reported
2022
Enrolled
557
Replication
Confirmed and extended by DESTINY-Breast06 (HER2-low and ultralow, chemotherapy-naive) with a near-identical PFS hazard ratio.

Outcomes

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In plain words
What these results mean for people, not percentages
557 people took part
Progression-free survival, HR+ cohort (BICR)primarysurrogate endpoint
  • Median 10.1 vs 5.4 months with Trastuzumab deruxtecan compared with Chemotherapy (TPC); about 4.7 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 49 percent lower chance of the event at any given time (hazard ratio 0.51, likely range 0.4 to 0.64).
  • 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.
Overall survival, all patientssurvival endpoint
  • Median 23.4 vs 16.8 months with Trastuzumab deruxtecan compared with Chemotherapy (TPC); about 6.6 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 36 percent lower chance of the event at any given time (hazard ratio 0.64, likely range 0.49 to 0.84).
  • Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
Progression-free survival, HR-negative (TNBC) cohortsurrogate endpoint
  • Median 8.5 vs 2.9 months with Trastuzumab deruxtecan compared with Chemotherapy (TPC); about 5.6 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 54 percent lower chance of the event at any given time (hazard ratio 0.46, likely range 0.24 to 0.89).
  • 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.
  • Exploratory cohort.
Be careful
  • These results apply to the people the trial enrolled: HER2-low metastatic breast cancer after chemotherapy: T-DXd vs chemotherapy. 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.

557 participants enrolled.

Progression-free survival, HR+ cohort (BICR)primary
HR 0.51 (0.4–0.64) · p <0.001
Trastuzumab deruxtecan
10.1 mo
Chemotherapy (TPC)
5.4 mo
Source
Overall survival, all patients
HR 0.64 (0.49–0.84) · p = 0.001
Trastuzumab deruxtecan
23.4 mo
Chemotherapy (TPC)
16.8 mo
Source
Progression-free survival, HR-negative (TNBC) cohort
HR 0.46 (0.24–0.89)
Trastuzumab deruxtecan
8.5 mo
Chemotherapy (TPC)
2.9 mo

Exploratory cohort

Source
EndpointArmnValueHR (95% CI)pSource
Progression-free survival, HR+ cohort (BICR)primaryTrastuzumab deruxtecan33110.1 months0.51 (0.4–0.64)<0.001link
Chemotherapy (TPC)1635.4 months
Overall survival, all patientsTrastuzumab deruxtecan37323.4 months0.64 (0.49–0.84)0.001link
Chemotherapy (TPC)18416.8 months
Progression-free survival, HR-negative (TNBC) cohortTrastuzumab deruxtecan408.5 months0.46 (0.24–0.89)link
Chemotherapy (TPC)182.9 months
Replication
Confirmed and extended by DESTINY-Breast06 (HER2-low and ultralow, chemotherapy-naive) with a near-identical PFS hazard ratio.

Key papers

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Connected

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