Precision medicine for advanced pancreas cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial — ASN Events
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  3. Precision medicine for advanced pancreas cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial

Precision medicine for advanced pancreas cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial (#268)

Lorraine Chantrill 1 , Adnan Nagrial 2 3 , Clare Watson 2 , Amber Johns 2 , Mona Martyn-Smith 2 , Skye Simpson 2 , Scott Mead 2 , Marc Jones 4 , Jaswinder Samra 5 , Anthony Gill 6 , Nicole Watson 6 , Venessa Chin 2 , Jeremy Humphris 2 , Angela Chou 2 , Belinda Brown 7 , Adrienne Morey 7 , David Thomas 2 , Lucille Sebastian 8 , katrin Sjoquist 8 , Sonia Yip 8 , Nick Pavlakis 9 , Ray Asghari 10 , Sandra Harvey 10 , Peter Grimison 11 , John Simes 8 , Andrew Biankin 4
  1. Macarthur Cancer Therapy Centre, Campbelltown, NSW, Australia
  2. Kinghorn Cancer Centre, Darlinghurst, NSW, Australia
  3. Crown Princess Mary Cancer Centre, Westmead, NSW, Australia
  4. Wolfson Wohl Cancer Research Centre, Glasgow, Scotland
  5. Pancreatobiliary Surgery, Northern Cancer Institute, St Leonards, NSW, Australia
  6. Anatomical Pathology, Royal North Shore Hospital, St Leonards, Sydney, NSW, Australia
  7. Anatomical Pathology, St Vincents Hospital, Darlinghurst, NSW, Australia
  8. Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
  9. Medical Oncology, Northern Cancer Institute, St Leonards, NSW, Australia
  10. Medical Oncology, Bankstown and Lidcombe Hospital, Bankstown, NSW, Australia
  11. Medical Oncology, Chris OBrien Lifehouse at RPA, Sydney, NSW, Australia

Background
The IMPaCT trial was designed to exploit results from whole genome sequencing of pancreatic cancer collected by the Australasian Pancreatic Genome Initiative under the auspices of the ICGC. Results showed that small subsets of patients had actionable changes in their tumor genome that could be druggable with currently available therapies. 7% of cases were found to be KRAS wildtype, and this phenotype may enrich for susceptibility to EGFR inhibition. Her2 amplification occurs in 2% and may confer sensitivity to Her inhibition. Tumors displaying defects in the DNA damage repair pathway (~5%) respond to DNA damaging chemotherapy.

Methods
The IMPaCT trial has recently been amended to a single arm pilot study of first line molecularly guided therapy for advanced pancreas cancer. Patients are permitted to begin their first cycle of chemotherapy with gemcitabine with or without nab-paclitaxel while awaiting molecular results. We screen potential patients for the three molecular targets described above.

Results
Using the WGS data, we constructed a custom sequencing panel to use DNA extracted from FFPE core biopsies to screen in real time for mutations in KRAS, BRCA2, BRCA1, PALB2 and ATM. Her2 screening is undertaken with IHC and FISH. We have screened almost 100 cases and found 22 relevant molecular targets. One patient with KRAS WT pancreas cancer is receiving gemcitabine in combination with erlotinib on the trial.

Conclusions
There is a dire need for more intelligent treatment selection in pancreas cancer and this pilot phase trial aims to demonstrate feasibility of such an approach.

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