Introduction: Pancreatic Cancer (PC) is the 3rd leading cause of cancer death. Precision-Panc UK Consortium was established to accelerate therapeutic development for PC by harmonizing the continuous learning between Discovery, Preclinical and Clinical Development, thereby overcoming the challenges of delivering precision medicine in PC.
Methods: Central to the Clinical Development is a Master Protocol (MP) to screen, biopsy, and molecularly profile patients for subsequent enrollment into multiple downstream PRIMUS clinical trials on the portfolio. Novel patient and tissue pathways were developed and incorporated into routine clinical practice to fast-track research activities, to enable clinically meaningful turnaround time for molecular profile. All profiling is performed on bespoke Glasgow Precision Oncology Laboratory Clinical Cancer Genome assay using targeted capture next generation sequencing (NGS) technology. NGS is performed in batches for the first 150 patients on PRIMUS trial, then in real-time thereafter.
Results: (Undated data to be presented if selected for presentation.) To date, 245 patients have entered the Precision-Panc study, of which 186 were registered on the MP, and 90 enrolled in PRIMUS trials. Patients not registered or subsequently not enrolled in PRIMUS trials were majority due to, alternative diagnosis (n = 16), declining performance status (n = 36), death (n = 21), or declined PRIMUS trials (n = 23). Of those declined, majority due to geography or wishing to start chemotherapy straight away. Two patients declined due to being germline BRCA carriers, and elected FOLFIRINOX. The median time between biopsy samples and DNA yield was 7 days (range 1 - 55). Of the first 100 donors confirmed to have PC on pathology QC, 21 underwent microdissection (cellularity < 15%), and 3 failed at DNA extraction QC (all had microdissection). Of the 97 donors with DNA (194 paired tumor/normal samples) submitted for sequencing (62 endoscopic ultrasound, 35 interventional radiology), 1/96 (1%) failed sequencing QC. KRAS mutation was not detected in 16 cases (17%), and out of these 8 did not have somatic variant and/or driver event identified indicating no tumor or low cellularity falling below the detection threshold of the sequencing and analysis pipeline. The other 8 cases with other driver events detected including actionable mutations such as NTRK1, and FGFR1 gain. In addition, 1 patient had TMB greater than 12 mut/MB. The NGS workflow is 10 working days turnaround. Each failed case was reviewed to identify causes and subsequent measures were made to prevent future occurrences.
Conclusion: We present the initial Precision-Panc experience of delivering precision medicine for PC in a national health care system, highlighting challenges associated with attrition along patient and tissue pathways. Majority of samples, obtained by either EUS or IR biopsies, were successfully sequenced. Embedding research activities into routine clinical practice significantly reduced time from sample to DNA yield.
Citation Format: David K. Chang, Susie Cooke, Stephan B. Dreyer, Jon Stobo, Fraser Duthie, Nigel Jamieson, Judith Dixon, Christine Wilshire, Nicola Williams, Colin J. McKay, Juan W. Valle, Andrew V. Biankin. Precision medicine for pancreatic cancer in national health care system: The initial Precision Panc experience [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 815.