June 2015, Vol 4, No 3
Genomic Sequencing for Pancreatic Cancer
Just because whole genome sequencing can be done on a patient’s tumor doesn’t mean that this will translate to a patient’s getting targeted therapy for
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. Results were presented at the 2015 Annual Meeting of the American Association for Cancer Research and published in Clinical Care Research.
Pancreatic cancer is particularly difficult to treat. The average lifespan if not treated is about 31 days, and 5-year survival is very poor. Thus, identification of targetable mutations might be a way to improve outcomes.
Of 93 patients screened in IMPaCT, 76 were eligible for whole genome sequencing. Of these, actionable targets were identified in 22 patients, and none went on to receive targeted therapy on the trial.
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 lab and back, short life span of pancreatic cancer patients, their desire not to be randomized if they have an identifiable genetic abnormality, urgency to get treatment as quickly as possible, and lack of teamwork among specialties involved.
The authors 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 author Lorraine A. Chantrill, MD, The 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 deaths due to pancreatic cancer.
Only 22 of those screened turned out to be candidate cases. Of the 22 patients with actionable targets identified, 6 died before results were obtained, and the other 16 could not get 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, Chantrill said.
At present, the cost of multiple gene panels is not reimbursed by insurance companies, which is yet another hurdle.
Targeted treatments have proved to be clinically successful and represent the realization of personalized medicine’s potential. In non–small cell lung cancer (NSCLC), molecularly targeted treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib have shown dramatic responses in patients with activating mutations.1-3 EGFR [ Read More ]
Case Studies: Incorporating Molecular Biomarkers into Therapy for Breast Cancer Is Fraught with Difficulty
Many therapeutic agents target HER2-positive breast cancer. Unfortunately, patient selection for these agents has not been refined, so all HER2-positive patients receive them. In estrogen receptor (ER)-positive disease, new agents improve the response to hormone-targeted therapies, but again, the appropriate patients for targeted agents have not been defined. “Because many [ Read More ]