Genomic Sequencing for Pancreatic Cancer Still Facing Hurdles
Philadelphia, PA—Although whole genomic sequencing can be done on a patient’s tumor, it does not mean that this will translate to a patient’s getting targeted therapy to identified genetic abnormalities, especially if that patient has pancreatic cancer.
In the Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial, no patient with an identified genetic abnormality proceeded to targeted therapy. The trial’s results were presented at the 2015 American Association for Cancer Research meeting and were simultaneously published in Clinical Cancer Research (Chantrill LA, et al. 2015;21:2029-2037).
Pancreatic cancer is particularly difficult to treat. If not treated, the average life span is approximately 31 days, and 5-year survival is very poor. Thus, the identification of targetable mutations may improve outcomes.
Of 93 patients screened in IMPaCT, 76 were eligible for whole genomic sequencing. Of these, actionable targets were identified in 22 patients, and none went on to receive targeted therapy in the trial.
The reasons cited for the failure to get patients to targeted therapy include difficulty in obtaining adequate tumor tissue for biopsy, lag time in getting tumor tissue to the laboratory and back, a short life span of patients with pancreatic cancer, the patients’ desire not to be randomized if they have an identifiable genetic abnormality, an urgency to get treatment as quickly as possible, and a lack of teamwork among the specialties involved.
The investigators suggested that healthcare systems are not set up for expediting genomic results. “We are in the middle of a learning curve. The technology is ahead of what our healthcare systems can deliver. It will take a long time for this to become a reality,” said lead investigator Lorraine A. Chantrill, BSC, MBBS, Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
The study screened for 3 molecular targets—HER2 amplification, KRAS wild-type, and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). Of the 76 patients screened, 17 were unsuitable for tissue processing for a variety of reasons, including ineligibility, objecting to randomization, and death from pancreatic cancer.
Only 22 of the screened patients were candidate cases. Of the 22 patients with actionable targets identified, 6 died before results were obtained, and the other 16 could not receive treatment for a variety of reasons.
To move the field along, the infrastructure has to change to incorporate the various specialties involved as a team, Dr Chantrill said.
At present, the cost of multiple gene panels is not reimbursed by insurance companies, which is yet another hurdle.