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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.
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.
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.
Shares Daiichi Sankyo, Trastuzumab deruxtecan, Biliary tract cancer (all types), HER2.
Shares Do-Youn Oh, HER2 IHC 3+ (HER2-positive by immunohistochemistry), Biliary tract cancer (all types), HER2.
Shares HER2 IHC 3+ (HER2-positive by immunohistochemistry), HER2, Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer, Pancreatic ductal adenocarcinoma.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer, Pancreatic ductal adenocarcinoma.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer, Pancreatic ductal adenocarcinoma.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer, Pancreatic ductal adenocarcinoma.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer, Pancreatic ductal adenocarcinoma.