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The 2020 trial of an enzyme meant to dissolve the dense matrix around pancreatic tumours so chemotherapy could reach them: more tumours shrank, but patients lived no longer, and the drug was abandoned.
HALO 109-301 was a phase 3, randomised, double-blind, placebo-controlled trial in untreated, metastatic, hyaluronan-high pancreatic ductal adenocarcinoma. Patients were randomised 2:1 to pegvorhyaluronidase alfa (PEGPH20, 3.0 micrograms per kilogram twice weekly in cycle 1 then weekly) plus nab-paclitaxel and gemcitabine, or placebo plus the same chemotherapy; 494 were randomised and 492 analysed (327 versus 165). With 330 deaths, median overall survival was 11.2 versus 11.5 months (hazard ratio 1.00, 95 percent confidence interval 0.80 to 1.27, P = 0.97); median progression-free survival 7.1 versus 7.1 months; objective response 47 versus 36 percent. Grade 3 or higher fatigue (16.0 versus 9.6 percent), muscle spasms (6.5 versus 0.6) and hyponatraemia (8.0 versus 3.8) were commoner with PEGPH20. The authors concluded the results do not support further development.
The definitive negative result for first-generation stromal targeting: a biomarker-selected population, a drug that did what it was designed to do to the matrix, and no survival benefit; the stroma ideas on this page start from here.
Shares Stroma-rich and desmoplastic tumours in molecular data, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, Desmoplasia (tumour stroma) and the tag pancreatic-evidence.
Shares Eric Van Cutsem, Gemcitabine + nab-paclitaxel, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Journal of Clinical Oncology and the tag pancreatic-evidence.
Shares Gemcitabine + nab-paclitaxel, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Journal of Clinical Oncology, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Gemcitabine + nab-paclitaxel, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Journal of Clinical Oncology, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.