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In 195 patients treated with chemotherapy for advanced pancreatic cancer, one in five had the basal-like type; those patients responded a third as often, progressed on FOLFIRINOX four times as often and lived 5.9 rather than 9.3 months, and a simple GATA6 tissue stain picked the type out.
Within COMPASS, patients proceeding to chemotherapy for advanced pancreatic ductal adenocarcinoma had biopsies RNA-sequenced. Between December 2015 and May 2019, 195 patients (95%) had enough tissue; 39 (20%) were basal-like and 156 (80%) classical. Among 157 with response data, the overall response rate was 10% in basal-like against 33% in classical (P = 0.02); in basal-like tumours treated with modified FOLFIRINOX the progression rate was 60% against 15% (P = 0.0002). Median overall survival was 9.3 months for classical against 5.9 for basal-like (hazard ratio 0.47; P = 0.0001). GATA6 expression by RNA sequencing correlated with the classifier and in situ hybridisation predicted subtype with sensitivity 89% and specificity 83%; GATA6 was prognostic in multivariate analysis. Basal-like tumours could be identified by keratin 5, were more hypoxic and enriched for a T-cell-inflamed signature.
It is the number behind 'basal-like is chemoresistant' and the validation of the GATA6 stain that lets a pathology laboratory call the subtype without RNA sequencing.
Shares COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection, GATA6 as the marker of classical versus basal-like pancreatic cancer, Ontario Institute for Cancer Research, Princess Margaret Cancer Centre.
Shares COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection, GATA6 as the marker of classical versus basal-like pancreatic cancer, Ontario Institute for Cancer Research, Princess Margaret Cancer Centre.
Shares Clinical Cancer Research, FOLFIRINOX / mFOLFIRINOX, RNA sequencing & expression profiling, Pancreatic ductal adenocarcinoma.
Shares COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection, GATA6 as the marker of classical versus basal-like pancreatic cancer, FOLFIRINOX / mFOLFIRINOX, Metastatic pancreatic ductal adenocarcinoma.
Shares Ontario Institute for Cancer Research, Princess Margaret Cancer Centre.
Shares Clinical Cancer Research, RNA sequencing & expression profiling, Pancreatic ductal adenocarcinoma.
Shares Ontario Institute for Cancer Research, Princess Margaret Cancer Centre.
Shares COMPASS: real-time sequencing of advanced pancreatic cancer for treatment selection, GATA6 as the marker of classical versus basal-like pancreatic cancer, Pancreatic ductal adenocarcinoma.