Abstract
PurposeRapid advances in the understanding of cancer biology have transformed drug development thus leading to the approval of targeted therapies and to the development of molecular tests to select patients that will respond to treatments. KRAS status has emerged as a negative predictor of clinical benefit from anti-EGFR antibodies in colorectal cancer, and anti-EGFR antibodies use was limited to KRAS wild type tumors. In order to ensure wide access to tumor molecular profiling, the French National Cancer Institute (INCa) has set up a national network of 28 regional molecular genetics centers. Concurrently, a nationwide external quality assessment for KRAS testing (MOKAECM) was granted to analyze reproducibility and costs.Methods96 cell-line DNAs and 24 DNA samples from paraffin embedded tumor tissues were sent to 40 French laboratories. A total of 5448 KRAS results were collected and analyzed and a micro-costing study was performed on sites for 5 common methods by an independent team of health economists.ResultsThis work provided a baseline picture of the accuracy and reliability of KRAS analysis in routine testing conditions at a nationwide level. Inter-laboratory Kappa values were >0.8 for KRAS results despite differences detection methods and the use of in-house technologies. Specificity was excellent with only one false positive in 1128 FFPE data, and sensitivity was higher for targeted techniques as compared to Sanger sequencing based methods that were dependent upon local expertise. Estimated reagent costs per patient ranged from €5.5 to €19.0.ConclusionThe INCa has set-up a network of public laboratories dedicated to molecular oncology tests. Our results showed almost perfect agreements in KRAS testing at a nationwide level despite different testing methods ensuring a cost-effective equal access to personalized colorectal cancer treatment.
Highlights
New therapeutic approaches such as anti-EGFR targeted therapies and concurrent identification of molecular biomarkers to identify sub-groups of potentially responsive tumors had created a need for routine molecular characterization of cancers
Our results showed almost perfect agreements in KRAS testing at a nationwide level despite different testing methods ensuring a costeffective equal access to personalized colorectal cancer treatment
This result was rapidly followed by a directive of the European Medicines Agency (EMEA) that restricted the use of cetuximab (ErbituxH) and panitumumab (VectibixH) to patients with KRAS wild-type metastatic colorectal cancer [2]
Summary
New therapeutic approaches such as anti-EGFR targeted therapies and concurrent identification of molecular biomarkers to identify sub-groups of potentially responsive tumors had created a need for routine molecular characterization of cancers. The demonstration that patients with KRAS mutated tumors did not benefit from anti-EGFR monoclonal antibodies was established independently of the technology used to identify KRAS mutated tumors [1]. This result was rapidly followed by a directive of the European Medicines Agency (EMEA) that restricted the use of cetuximab (ErbituxH) and panitumumab (VectibixH) to patients with KRAS wild-type metastatic colorectal cancer [2]. The French government and the National Cancer Institute (INCa) have set up a national network of 28 regional molecular genetics centers to implement routine molecular testing for colorectal cancer. More than one laboratory can be related to one regional center
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