Abstract 93: Molecular profiling of pancreatic cancer patients from a wide geographical distribution across the US

Abstract

Commercial genomic and protein-based profiling was performed on tissue from pancreatic cancer patients who enrolled in the Pancreatic Cancer Action Network's Know Your Tumor (KYT) service. The service offers molecular profiling for patients with resectable or metastatic disease, in preparation for their next treatment plan. Patients are eligible to enroll at any institution, clinic, or cancer center in the US. Biopsies, tissue retrieval and testing is coordinated by Perthera, Inc.

From 6/2014 to 11/2015 tumor biopsies, resected or archived tissue was obtained from 152 (53% male) pancreatic cancer patients and profiling including NGS/FISH (144 patients) and IHC (143 patients) was performed. The median age at biopsy or resection was 63 (25-83), 55% of the tissue came from liver, 16% from pancreas, 7% lung, 4% peritoneum, and 18% from another type of tissue. 87% of the patients were diagnosed with pancreatic ductal adenocarcinoma and the remaining with another form of confirmed or suspected pancreatic cancer.

The most identified pathogenic mutations were KRAS (85%), TP53 (72%), CDKN2A (47%), CDKN2B (24%), SMAD4 (22%), ARID1A (10%), STK11 (7%), and BRCA2 (5%). The average number of genomic alterations (likely but not confirmed to be somatic) detected was five per patient from a panel of 320 genes. Molecular modifications that are linked to a treatment option were observed in 44% of patients. Twenty four of 144 patients (17%) had mutations in at least one DNA repair gene potentially benefiting from platinum or PARP inhibitor-based therapies, including BRCA2 (5%), ATM (4%), BAP1 (4%), SMARCA4 (3%), FANC (1%), CHEK2 (1%), and PALB2 (<1%). Other actionable molecular phenotypes observed include anti-HER2 therapies targeting ERBB2 amplifications (3%) and mTOR inhibitors suitable for patients with mutations in STK11/LKB1 (7%), PTEN (3.5%), PIK3R1 (<1%), or PIK3CA (3%). Actionable alterations identified with a low frequency (<2%) include RET fusions, amplifications of FGFR, CRKL, AXL, and mutations in NTRK3, MEN1 (PNET), and BRAF. One patient harbored the BRAF V600E mutation, prompting consideration of off label melanoma-approved therapy. Overexpression of ALK by IHC was observed in one patient who chose to enroll in a ceritinib clinical trial. Six percent of patients were PDL-1 positive, and 22% were positive for PD-1 from tumor infiltrating lymphocytes, suggesting possible activity from immune checkpoint inhibitors.

To date, 7 of the 152 patients have enrolled in a clinical trial, 4 were treated with an off label treatment, 67 have yet to make their next treatment decision, and 53 are known to be deceased. KYT has successfully profiled tumors and presented targeted treatment options to patients and physicians in 33 states regardless of a patient's socioeconomic background and geographic location, moving the field a step closer towards a democratized, personalized approach to treating pancreatic cancer.

Citation Format: Lola Rahib, Anitra Engebretson, Michael J. Pishvaian, Jonathan R. Brody, William A. Hoos, Emily E. Lyons, Joseph Bender, Emanuel F. Petricoin, Subha Madhavan, Craig Heartwell, Lynn M. Matrisian. Molecular profiling of pancreatic cancer patients from a wide geographical distribution across the US. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 93.