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DESTINY-Lung02 confirmed that the antibody-drug conjugate trastuzumab deruxtecan shrinks about half of HER2-mutant lung cancers after chemotherapy and that the lower dose works as well with less lung inflammation.
DESTINY-Lung02 randomised 152 patients with metastatic HER2-mutant non-small-cell lung cancer that had progressed after platinum chemotherapy to trastuzumab deruxtecan at 5.4 mg/kg or 6.4 mg/kg every three weeks. DESTINY-Lung01 had shown a 55 percent response rate at 6.4 mg/kg but with interstitial lung disease in a quarter of patients.
The confirmed response rate was 49.0 percent at 5.4 mg/kg (102 patients) and 56.0 percent at 6.4 mg/kg (50 patients), with median durations of response of 16.8 and 5.9 months. Drug-related interstitial lung disease occurred in 12.9 percent at the lower dose and 28.0 percent at the higher dose.
The FDA had granted accelerated approval in August 2022 on the interim data, the first HER2-directed therapy for lung cancer, at the 5.4 mg/kg dose; DESTINY-Lung04 is testing the drug first line against chemotherapy plus pembrolizumab.
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.
152 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Confirmed objective response rateprimary | Trastuzumab deruxtecan 5.4 mg/kg | 102 | 49% | - | - | link |
| Trastuzumab deruxtecan 6.4 mg/kg | 50 | 56% |
This is the paper Europe PMC returns for registry id NCT04644237 with the most citations, so it is the natural first reading for anyone following the DESTINY-Lung02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
Trastuzumab deruxtecan 5.4 mg/kg is the approved regimen for HER2-mutant lung cancer after platinum chemotherapy, and the trial is a rare example of dose optimisation improving safety without losing efficacy.
Shares HER2-mutant non-small-cell lung cancer, Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads).
Shares HER2-mutant non-small-cell lung cancer, Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads).
Shares Interstitial lung disease (ILD) / pneumonitis, Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads).
Shares HER2-mutant non-small-cell lung cancer, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), AstraZeneca.
Shares HER2-mutant non-small-cell lung cancer, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), AstraZeneca.
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), AstraZeneca.
Shares Daiichi Sankyo, Topoisomerase-I inhibitors (and ADC payloads), AstraZeneca, Antibody-drug conjugate (ADC).
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), AstraZeneca.