• melanoma
• colorectal cancer
• lung cancer

Several studies recently reported about the good performances of the Idylla molecular diagnostic platform (Biocartis, Mechelen, Belgium) as a fast and fully automated real-time quantitative PCR cartridge-based tool to diagnose oncogenic mutations in colorectal cancer, lung cancer and melanoma.1–3 The cost-effectiveness of implementing Idylla in molecular diagnostics laboratories remains to date uncertain and few investigated. Colling et al reported about the valuable performances of the new Idylla NRAS-BRAF-EGFRS492R Mutation Assay in combination with the Idylla KRAS Mutation Test in colorectal cancer. Nevertheless, taking into account the financial implications of using Idylla platform in the UK, Colling et al mentioned that using Idylla in an established molecular diagnostics laboratory may not be cost-effective in comparison with next-generation sequencing (NGS).1 Financial implications could be different from one healthcare system to another. Besides UK data reported by Colling et al, we considered the financial implications of using Idylla from a French healthcare system point of view. In this evaluation, we took into account the proposed prices of cancer-related molecular tests in France, the reported excellent performances of Idylla platform in detecting panels of KRAS, NRAS, BRAF and EGFR mutations (see www.biocartis.com for mutation panels for different Idylla cartridges) and the frequencies of these Idylla-detectable mutations encountered about colorectal cancer, non-small cell lung cancer (NSCLC) and melanoma tumour samples in our daily practice in patients with advanced cancers.1–5

In France, the price of an NGS analysis using a gene-panel approach is proposed at €882.9. This approach could be used to search for KRAS, NRAS and BRAF mutations in colorectal cancers, EGFR and KRAS mutations in lung cancers or BRAF and NRAS mutations in melanomas with the same price.4

In the field of metastatic colorectal cancer, the price of a KRAS-NRAS restricted analysis is proposed in France at €440.1 per sample.5 The cartridge-related cost of Idylla NRAS-BRAF-EGFRS492R Mutation Assay (or an Idylla NRAS-BRAF Mutation Test) in combination with Idylla KRAS Mutation Test is about €372 for a combination able to detect more than 95% of the RAS mutations detected in colorectal cancer in our experience. Considering that about 52% of colorectal cancers harbour a RAS mutation (46% of KRAS and 6% of NRAS mutations in our daily practice), among 100 colorectal cancer samples, Idylla would detect a RAS mutation in 50 samples and second-line NGS analyses in 50 Idylla wild-type samples would permit to detect RAS mutations in two additional samples. The cost of analysing 100 samples with the single NGS approach would be €88 290 whereas the cost of a combined approach based on first-line Idylla analysis followed by NGS analysis in case of Idylla-RAS wild-type result would be €88 155 (ie, €44 010 for 100 Idylla analyses plus €44 145 for NGS analyses of 50 samples). As a result, using Idylla as a first-line analysis would not increase the cost of analyses in comparison with a single NGS approach in a set of 100 colorectal cancer samples. In this manner, from a French healthcare system point of view, using Idylla to analyse colorectal cancer samples could be a cost-effective approach even in established molecular diagnostics laboratory with access to NGS.

EGFR-KRAS restricted mutation testing in metastatic NSCLC is proposed at €459 per sample in France.5 The cartridge-related cost of Idylla EGFR Mutation Assay in combination with Idylla KRAS Mutation Test is about €396 for a test combination able to detect about 90% of the EGFR and KRAS mutations detected in NSCLC in our experience. Considering that EGFR and KRAS mutations are nearly mutually exclusive in NSCLC and that they respectively concern about 10% and 30% of NSCLC-analysed samples in our daily practice, analysing 100 NSCLC samples with Idylla would permit to detect a EGFR or KRAS mutation in 36 samples for a cost of €45 900 and performing additional NGS analyses in the 64 Idylla wild-type samples would detect four additional mutations for an NGS-related cost of €56 506. Facing with the cost of a single NGS approach (€88 290), the cost of a first-line Idylla testing followed by NGS analysis in case of Idylla wild-type result would be €102 406, that is, an additional cost of €14 116. Therefore, a systematic screening of NSCLC using Idylla would not be a cost-effective approach in NSCLC in an approach combining Idylla with NGS. Nevertheless, using Idylla testing could remain an interesting ancillary tool for rapid molecular status and treatment choices in patients with metastatic NSCLC suffering from acute deterioration.2

In the field of metastatic melanoma, a BRAF-NRAS restricted analysis is proposed at €329.4 per sample in France.5 The cost of an Idylla cartridge in this field is about €216 (Idylla NRAS-BRAF Mutation Test or Idylla NRAS-BRAF-EGFRS492R Mutation Assay). Idylla NRAS and BRAF testing allows the detection of about 95% of the NRAS and BRAF mutations encountered in our daily practice in patients with metastatic melanomas (consisting of 25% of NRAS-mutated and 35% of BRAF-mutated melanomas in our institution). Among 100 melanoma samples, Idylla would permit to detect a BRAF or NRAS mutation in about 57 samples for €32 940 whereas second-line NGS analyses in the 43 Idylla wild-type samples would cost €37 968 to detect three additional mutations. The global cost of this approach (€70 908) is inferior to the cost of single NGS approach (€88 290 for 100 samples), and using Idylla is in this manner a cost-effective approach in melanoma for patients with acute deterioration and in a routine workflow.3

In colorectal cancer, lung cancer and melanoma samples, a low number of additional mutations would be detected by second-line NGS analyses after a first-line Idylla negative test (two to four mutants per 100 tumour samples). This raises the questions of a second-line NGS analysis and of a molecular diagnostic strategy entirely based on a single Idylla testing, without second-line NGS rescue technique. On the one hand, a single Idylla approach would result in a massive decrease in the costs of cancer-related molecular tests (about half of the costs of current NGS analyses in the mentioned examples of colorectal cancer, lung cancer and melanoma). On the other hand, a single Idylla approach could miss a proportion of patients who could potentially benefit from targeted therapies. Nevertheless, some rare mutants detected by NGS but not using Idylla are not clearly clinically relevant for treatment choices. Further studies are needed to evaluate the interest of detecting these Idylla non-detectable rare mutants from a response to treatment point of view. In case of poor clinical relevance of these rare mutants, we believe that Idylla could consist of an alternative and stand-alone molecular diagnostic method searching for KRAS, NRAS, BRAF and EGFR mutations in tumour samples.

In our analysis, we only focused on the prices of the cancer-related molecular tests themselves in France. Nevertheless, other medicoeconomic key advantages of the Idylla platform have to be heavily considered. Indeed, in comparison with NGS, using Idylla allows easier and quicker sample preparation (less than 2 min) and molecular result delivery (in less than 4 hours vs many days to weeks using NGS) permitting rapid treatment choices and optimised patients' care path. Moreover, the costs and technical constraints linked to the implementation of an Idylla system in a laboratory are greatly inferior to those corresponding to NGS. In this manner, the implementation of Idylla could be affordable for more numerous pathology laboratories limiting the need of centralised molecular testing. Further evaluations are needed to confirm and quantify the medicoeconomic interest of Idylla testing through the calculation of the incremental cost-effectiveness ratio given global health care-related costs and effects at the level of the patients' care path and therapeutic management.

To conclude, in our opinion, according to the prices currently proposed in France for cancer-related molecular tests, implementing a fast and fully automated molecular theranostic Idylla platform in a molecular pathology laboratory could be an interesting strategy from a medicoeconomic point of view. Its use as an emergency-restricted test (NSCLC), as a routine first-line and workflow-useable tool (colorectal cancer and melanoma) or even as a single molecular diagnostic method could be valuable and has to be considered from the point of view of each laboratory and each healthcare system to determine the best place of this new tool beside the growing field of cost and time-consuming NGS analyses.