Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract or pancreatic tumors: a subgroup analysis of DESTINY-PanTumor02
In the tumour-agnostic trial that led to the HER2 IHC 3+ approval, trastuzumab deruxtecan shrank about a quarter of 41 pretreated biliary cancers overall and more than half of those with the strongest HER2 stain, while pancreatic tumours barely responded.
Overview
DESTINY-PanTumor02 (NCT04482309) Part 1 evaluated trastuzumab deruxtecan 5.4 mg/kg in locally advanced or metastatic HER2 IHC 3+ or 2+ tumours (local or central testing) that had progressed after systemic treatment or had no treatment options. The primary endpoint was investigator-assessed objective response rate; this report covers the biliary tract (41 patients) and pancreatic (25 patients) cohorts, with median follow-up of 6.0 and 5.0 months.
By investigator, objective response rate was 22.0% (95% CI 10.6 to 37.6) in biliary tract cancer and 4.0% (0.1 to 20.4) in pancreatic cancer; by independent central review 26.8% and 12.0%. Responses were seen across most biliary subgroups, with the highest rate, 56.3% (95% CI 29.9 to 80.2), in centrally confirmed HER2 IHC 3+ tumours. Stable disease was the best response in 61.0% of the biliary cohort; median overall survival was 7.0 months (95% CI 4.6 to 10.2). Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 17.1% of biliary patients and 4.0% of pancreatic patients.
- Biliary cohort (n = 41): objective response rate 22.0% by investigator, 26.8% by central review; 56.3% in centrally confirmed IHC 3+ tumours.
- Pancreatic cohort (n = 25): 4.0% by investigator.
- Interstitial lung disease or pneumonitis in 17.1% of biliary patients; median overall survival 7.0 months.
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.
- Subgroup of a single-arm basket study; local and central HER2 testing were both allowed.
- Short follow-up and small IHC 3+ subgroup (16 patients).
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