Personalizing Therapy
In 2018, the NCCN updated its guidelines to recommend that all individuals with a diagnosis of pancreatic cancer (and their family members) undergo genetic testing, regardless of family history or ethnic background, to identify inherited mutations.
“Patients with metastatic pancreatic cancer that also have germline BRCA mutation are now eligible for the PARP inhibitor olaparib, as it has been shown to extend progression-free survival. The National Comprehensive Cancer Network has incorporated this drug in their guidelines,” Mehdi said. Up to 7% of patients with pancreatic cancer have an inherited BRCA mutation.
Results from a Phase 3 randomized clinical trial presented in June at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine found that first-line platinum-based chemotherapy followed by maintenance therapy with olaparib doubled the time to disease progression in metastatic pancreatic cancer patients with a germline BRCA mutation.2
The median duration of response to olaparib was more than two years, with 22.1% of patients having no disease progression at 24 months. “While overall survival data are not yet mature, this is a significant advance given that the median survival of metastatic pancreatic cancer is currently less than one year,” ASCO said in a release.
“Gene profiling of tumor tissue is highly recommended,” as well, Mehdi noted.
Researchers at the University of Pittsburgh found that 17% of pancreatic cancers had actionable mutations. Fourteen percent had biomarkers that indicated alterations in the DNA damage repair pathway, which increases the likelihood of response to platinum-based chemotherapy regimens such as FOLFIRINOX or gemcitabine plus cisplatin as well as to PARP inhibitors.3
“Immunotherapy has mostly been disappointing but NCCN recommends considering pembrolizumab in select [microsatellite instability]-high tumors,” Mehdi added.
- Azar I, Virk G, Esfandiarifard S, Wazir A, Mehdi S. Treatment and survival rates of stage IV pancreatic cancer at VA hospitals: a nation-wide study. J Gastrointest Oncol. 2019 Aug;10(4):703-711.
- Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O’Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019 Jul 25;381(4):317-327.
- Singhi AD, George B, Greenbowe JR, Chung J, Suh J, Maitra A, Klempner SJ, Hendifar A, Milind JM, Golan T, Brand RE, Zureikat AH, Roy S, Schrock AB, Miller VA, Ross JS, Ali SM, Bahary N. Real-Time Targeted Genome Profile Analysis of Pancreatic Ductal Adenocarcinomas Identifies Genetic Alterations That Might Be Targeted With Existing Drugs or Used as Biomarkers. Gastroenterology. 2019 Jun;156(8):2242-2253.e4.