Challenges with genomic testing in pancreaticobiliary cancers: Results of a prospective cohort study.

Abstract

314 Background: Therapeutic options for advanced pancreaticobiliary (PB) malignancies may be improved by genomics-driven therapies. We conducted a prospective cohort study of outpatient genomic testing to identify prevalence of actionable alterations and therapeutic impact of such testing in PB cancers. Methods: Eligibility requirements included confirmed pathologic diagnosis of select solid tumor malignancies without a known curative option, age ≥ 18 years, and an ECOG performance status of 0-2. Data for the PB cancer subgroup are presented here. Tumor samples were sequenced for up to 315 candidate genes in collaboration with Foundation Medicine, Inc. (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board that made therapeutic recommendations to treating physicians. Results: From Aug 2013 to Aug 2014, samples from 228 patients were analyzed; 24 (11%) had PB cancers. For the latter subgroup, median age was 60 years; 14 (58%) were male; 20 (83%) were white. Twelve (50%) tumors were pancreatic, 11 (46%) from biliary tract/gallbladder, and 1 (4%) periampullary. Median time from consent to result was 24 (range, 3-84) days. Eight (33%) samples had inadequate tissue compared with 6/174 (3%) non-PB samples (p<0.001). Among patients with adequate tissue (n=16), a median of 3 (1-7) mutations were detected per sample; TP53 (50%), CDKN2A/p16 (44%) and KRAS (38%) were most common. A targeted therapy was recommended in 7 (44%) patients. Of these, 78% of recommendations were for specific clinical trials. To date, no patient with PB cancer has received a targeted therapy, compared with 6/45 (13%) patients with colorectal cancer (p=0.18). The most common reason for non-receipt of recommended targeted therapy was non-availability of clinical trials. Conclusions: Compared with other common solid tumors, genomic profiling in pancreaticobiliary cancers is challenged by paucity of diagnostic tissue collected during routine clinical care. Targeted therapy options (on-study or off-label) are few at this time. Precision oncology in pancreaticobiliary cancers will remain under-utilized until access to clinical trials is enhanced.