Performance and Cost Efficiency of KRAS Mutation Testing for Metastatic Colorectal Cancer in Routine Diagnosis: The MOKAECM Study, a Nationwide Experience

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.

KRAS mutation testing of metastatic colorectal cancer in Australia: Where are we at?

“…The present results were obtained using several different platforms, thus supporting our previous multicenter blinded study that found comparable results when different techniques were used in experienced laboratories . A nationwide French study also found excellent concordance between test results from 40 laboratories despite the use of five different methods . Although too numerous to list here, the great majority of publications on KRAS mutation in CRC have reported frequencies that lie within the range of 34–42%.…”

The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation

“…There is limited published evidence on the accuracy of RAS mutation tests. One study, by Blons et al, 189 conducted in France on KRAS testing, compared several testing techniques; the results for tests used in more than one laboratory are reproduced in Table 162. The results show that, even with high levels of dilution, the sensitivity and specificity remain quite high, in accordance with the tests' limits of detection.…”

“…This included several different testing techniques in terms of the number of exons tested and the types of tests used. 190 This study summarises part of the work conducted by the 189 suggesting that the accuracy of testing for RAS mutations may not differ significantly from the accuracy of testing for KRAS mutations. It also suggests that testing may be fairly consistent, despite the wide range of techniques used.…”

Enabling Equal Access to Molecular Diagnostics: What Are the Implications for Policy and Health Technology Assessment?

“…The French screening and targeted cancer treatment initiative offers equal access to molecular testing for all patients in France and represents a real benefit in terms of public health. It illustrates that molecular stratification can be successfully integrated into the health care system and, as an additional benefit, is a cost-effective strategy [39,40]. …”