Comprehensive genomic profiling for patients with chemotherapy-naïve advanced cancer

Abstract

Comprehensive genomic profiling (CGP) testing by next-generation sequencing has been introduced into clinical practice as part of precision cancer medicine to select effective targeted therapies. However, whether CGP testing at the time of first-line chemotherapy could be clinically useful is not clear. We conducted this single-center, prospective, observational study to investigate the feasibility of CGP testing for chemotherapy-naïve patients with stage III/IV gastrointestinal cancer, rare cancer, and cancer of unknown primary, using the FoundationOne^® companion diagnostic (F1CDx) assay. The primary outcome was the detection rate of at least one actionable/druggable cancer genomic alteration. Actionable/druggable cancer genomic alterations were determined by the F1CDx report. An institutional molecular tumor board determined the molecular-based recommended therapies. A total of 197 patients were enrolled from October 2018 to June 2019. CGP success rate was 76.6% (151 of 197 patients), and median turnaround time was 19 days (range: 10-329 days). Actionable and druggable cancer genomic alterations were reported in 145 (73.6%) and 124 (62.9%) patients, respectively. The highest detection rate of druggable genomic alterations in gastrointestinal cancers was 80% in colorectal cancer (48 of 60 patients). Molecular-based recommended therapies were determined in 46 patients (23.4%). CGP testing would be a useful tool for the identification of a potentially effective first-line chemotherapy.

Keywords: actionable genomic alteration; comprehensive genomic profiling; druggable genomic alteration; gastrointestinal cancer; precision cancer medicine.

FIGURE 1

Trial profile. Passed report was defined as reports with results of all items examined. Qualified report was defined as reports which may have reduced sensitivity when the specimen does not meet performance specifications. pts, patients; FFPE, formalin‐fixed paraffin‐embedded.

FIGURE 2

Detection rate of actionable/druggable cancer genomic alterations and molecular‐based recommended therapies

FIGURE 3

Frequency of representative druggable cancer genomic alterations. The vertical axis shows the list of representative druggable cancer genomic alterations categorized by the pathway analysis. The heatmap value represents the frequency of “number of druggable cancer genomic alterations” divided by “number of patients” in each cancer type. BTC, biliary tract cancer; CRC, colorectal cancer; CUP, cancer of unknown primary; EC, esophageal cancer; GC, gastric cancer; GPCR, G protein–coupled receptor; MAPK, mitogen‐activated protein kinase; PC, pancreatic cancer; RC, rare cancer; TGF‐β, transforming growth factor beta.