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DESTINY-PanTumor02 gave the HER2-directed antibody-drug conjugate Enhertu to 267 patients in seven cohorts of HER2-expressing solid tumours, endometrial and cervical cancer among them. Endometrial cancer responded best, and in April 2024 the FDA granted the first tumour-agnostic HER2 approval, for tumours with the strongest HER2 staining and no satisfactory alternative.
DESTINY-PanTumor02, trial NCT04482309 sponsored by AstraZeneca and Daiichi Sankyo and published in JCO in 2024, showed that trastuzumab deruxtecan shrinks tumours across seven cohorts of HER2-expressing cancers, with endometrial cancer among the best responders, leading to the first tumour-agnostic HER2 approval. It was a phase 2 of 267 patients with HER2 IHC 2+ or 3+ solid tumours in seven cohorts; the endometrial cohort responded in 57.5 percent overall and 84.6 percent of IHC 3+ cases, the cervical cohort in half, and FDA accelerated approval followed in April 2024 for HER2 IHC 3+ solid tumours with no satisfactory alternative. HER2 testing is now recommended in serous endometrial carcinoma, and how far the tumour-agnostic label should reach is the open question.
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.
267 enrolled.
95% CI 24.4 to 67.8; duration of response range 2.1 to 22.0 months
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Objective response rate, endometrial cohortprimary | T-DXd (all HER2 IHC 2+/3+) | 40 | 57.5% | - | - | link |
| T-DXd (IHC 3+ only) | 13 | 84.6% | ||||
| Objective response rate, cervical cohort | T-DXd (all) | 40 | 50% | - | - | link |
| Confirmed objective response by independent central review, biliary tract cancer cohort with HER2 IHC 3+ (Enhertu label) | Trastuzumab deruxtecan (biliary tract, IHC 3+) | 22 | 45.5% | - | - | link |
The IHC 3+ subgroup result is why the tumour-agnostic label is written at 3+ and not 2+, and why a gallbladder cancer with a strong HER2 stain now has two on-label choices (zanidatamab, trastuzumab deruxtecan) after chemotherapy. Lung toxicity again ran higher than in breast cancer.
HER2 immunohistochemistry is now worth doing in advanced gynaecological and other cancers, since trastuzumab deruxtecan is approved for HER2 3+ solid tumours after prior therapy.
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Biliary tract cancer (all types), HER2.
Shares p53-abnormal endometrial cancer, including uterine serous carcinoma, Advanced or recurrent endometrial cancer, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads).
Shares Tumour-agnostic (tissue-agnostic) approval, Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads).
Shares Tumour-agnostic (tissue-agnostic) approval, Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads).
Shares Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer, Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials, Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types).
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Topoisomerase-I inhibitors (and ADC payloads), Endometrial cancer.
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.