Whole genome and transcriptome profiling in advanced pancreatic cancer patients on the COMPASS trial
Jennifer J. Knox, Gun Ho Jang, Robert C. Grant, Amy X. Zhang, Lucy Ma, Elena Elimova, Raymond Jang, Malcolm J. Moore, James Biagi, Mustapha Tehfé, Ravi Ramjeesingh, Erica S. Tsang, Spring Holter, Stephanie Ramotar, Shawn Hutchinson, Sheng‐Ben Liang, Ilinca M. Lungu, Shari Moura, Yifan Wang, Sheron Perera, Michelle Chan‐Seng‐Yue, Maryam Monajemzadeh, Kyaw Lwin Aung, Rebecca M. Prince, Joan Miguel Romero, Jesús Fuentes‐Antrás, Galileo Arturo Gonzalez Conchas, Sarah Picardo, Ricardo González, Sangeet Ghai, Korosh Khalili, Tae Kyoung Kim, Karen Ng, John M.S. Bartlett, Trevor J. Pugh, Sangeetha Kalimuthu, Sandra E. Fischer, Julie M. Wilson, Anna Dodd, George Zogopoulos, Barbara T. Grünwald, Faiyaz Notta, Steven Gallinger, Grainne M. O’Kane
Abstract
Integrated whole genome and transcriptome sequencing can unveil distinct molecular subgroups in pancreatic cancer (PDAC). The COMPASS trial (NCT02750657) enrolled 268 patients with advanced PDAC; patients were given either modified (m) FOLFIRINOX or Gemcitabine-nab-paclitaxel (GnP) as per physicians choice. Median follow-up is 52 months and median overall survival in those receiving mFOLFIRINOX is 10.6 months and 8.4 months for GnP. KRAS specific mutants and allelic states alone are not prognostic; however basal-like PDAC are more likely to harbour major imbalances in mutant KRAS (KRASmaj). In the presence of KRASmaj, pre-existing type II DM is more common. Distinct prognostic cohorts include homologous-recombination deficient PDAC, predictive of mFOLFIRINOX response. Basal-like PDAC and patients exhibiting evidence of systemic inflammation as annotated using the Gustave Roussy Immune Score are unique poor prognostic cohorts. The latter associates with low CD8 T cell infiltration while basal-like PDAC documents an inflamed tumour microenvironment. The COMPASS trial is a prospective observational study seeking to establish biomarkers in advanced pancreatic cancer through in-depth profiling prior to commencing chemotherapy. Here, the authors report the final data for the complete cohort of 268 patients enrolled in the COMPASS trial.