Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer: Early Results from the COMPASS Trial
Prospective genomic profiling of advanced pancreatic ductal adenocarcinoma (PDAC) is feasible, and early data indicate that chemotherapy response differs among patients with different genomic/transcriptomic subtypes.
**Purpose** To perform real-time whole genome sequencing (WGS) and RNA sequencing (RNASeq) of advanced pancreatic ductal adenocarcinoma (PDAC) to identify predictive mutational and transcriptional features for better treatment selection. **Experimental Design** Patients with advanced PDAC were prospectively recruited prior to first-line combination chemotherapy. Fresh tumor tissue was acquired by image-guided percutaneous core biopsy for WGS and RNASeq. Laser capture micro-dissection was performed for all cases. Primary endpoint was feasibility to report WGS results prior to first disease assessment CT scan at 8 weeks. The main secondary endpoint was discovery of patient subsets with predictive mutational and transcriptional signatures. **Results** Sixty-three patients underwent a tumor biopsy between December 2015 and June 2017. WGS and RNASeq were successful in 62 (98%) and 60 (95%), respectively. Genomic results were reported at a median of 35 days (range, 19–52 days) from biopsy, meeting the primary feasibility endpoint. Objective responses to first-line chemotherapy were significantly better in patients with the classical PDAC RNA subtype compared with those with the basal-like subtype (P = 0.004). The best progression‑free survival was observed in those with classical subtype treated with m‑FOLFIRINOX. GATA6 expression in tumor measured by RNA in situ hybridization was found to be a robust surrogate biomarker for differentiating classical and basal‑like PDAC subtypes. Potentially actionable genetic alterations were found in 30% of patients. **Conclusions** Prospective genomic profiling of advanced PDAC is feasible, and our early data indicate that chemotherapy response differs among patients with different genomic/transcriptomic subtypes.
These findings demonstrate that real‑time genomic and transcriptomic profiling can be performed within a clinically relevant timeframe for patients with advanced pancreatic cancer, enabling precision treatment decisions by identifying biomarkers that predict differential responses to standard chemotherapy regimens.
Bizonyítékszint: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.