BackgroundTreatment options for patients with metastatic colorectal cancer (mCRC) include anti-epithelial growth factor therapies, which, in Europe, are indicated in patients with RAS wild-type tumours only and require prior mutation testing of “hot-spot” codons in exons 2, 3 and 4 of KRAS and NRAS. The aim of this study was to evaluate the implementation of RAS testing methods and estimate the RAS mutation prevalence in mCRC patients.MethodsOverall, 194 pathology laboratories were invited to complete an online survey. Participating laboratories were asked to provide information on their testing practices and aggregated RAS mutation data from 20 to 30 recently tested patients with mCRC.ResultsA total of 96 (49.5 %) laboratories across 24 European countries completed the survey. All participants tested KRAS exon 2, codons 12 and 13. Seventy (72.9 %) laboratories reported complete testing of all RAS hot-spot codons, and three (3.1 %) reported only testing KRAS exon 2. Sixty-nine (71.9 %) laboratories reported testing >80 patients yearly for RAS mutation status. Testing was typically performed within the reporting institution (93.8 %, n = 90), at the request of a treating oncologist (89.5 %, n = 85); testing methodology varied by laboratory and by individual codon tested. For laboratory RAS testing, turnaround times were ≤10 working days for the majority of institutions (90.6 %, n = 87). The overall crude RAS mutation prevalence was 48.5 % (95 % confidence interval: 46.4–50.6) for laboratories testing all RAS hot-spot codons. Prevalence estimates varied significantly by primary tumour location, approximate number of patients tested yearly and indication given for RAS testing.ConclusionOur findings indicate a rapid uptake of RAS testing in the majority of European pathology laboratories.

Aim: A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. Materials & methods: Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. Results: The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources. Conclusion: The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research. Colorectal cancer (CRC) was the third most common malignancy among men and the second most common malignancy among women globally in 2012 [1]. Approximately, 60% of CRC cases occur in developed regions and incidence rates can vary up to tenfold around the world, with the lowest rates observed in South Central Asia and Africa (excluding Southern Africa) [2]. A quarter of patients with CRC already have metastatic disease at the time of their initial presentation and diagnosis, and almost 50% will subsequently develop metastases [3]. Once

513 Background: Guidelines for prescribing anti-EGFR therapy for metastatic colorectal cancer (mCRC) require prior testing to confirm RAS (exons 2, 3, 4 of KRAS and NRAS) wild-type status in Europe and the USA. There is limited published evidence reporting the prevalence of RAS mutations in patients with mCRC in a real-world setting. The aim of this study was to use data from a range of real-world sources to obtain RAS mutation prevalence estimates for different geographic regions. Methods: Aggregated RAS mutation prevalence data were collected from 13 sources, including individual pathology centers (n = 7), mCRC registries (n = 3), and Amgen-sponsored studies (n = 3). Data sources included in this study originated in Europe (n = 10), the Middle East (n = 2), and South America (n = 1). A meta-analysis of all collected data was carried out to investigate the effect of heterogeneity amongst the data sources and obtain pooled RAS prevalence estimates for each, using a mixed regression model. Results: Aggregate data from 4322 patients with mCRC were included in the pooled meta-analysis. The overall RAS mutation prevalence across all data sources was estimated to be 43.5% (95% CI: 41.5–45.5%). RAS mutation prevalence varied between data sources, ranging from low estimates of 33.7% (95% CI: 28.4–39.3%) for a Middle Eastern pathology dataset, and 34.6% (95% CI: 27.7–42.1%) for a Middle Eastern mCRC registry, to the highest estimates of 53.6% (95% CI: 43.2–63.8%) and 54.1% (95% CI: 51.7–56.5%) in two European pathology centers, in the Czech Republic and Poland, respectively. Conclusions: This is one of the first studies to carry out a large pooled analysis of RAS mutation prevalence, based on real-world data. There was a high degree of heterogeneity between the sources included, possibly due to the types of data source, patient selection criteria, geographic location, or differences in laboratory testing methods. The estimated RAS mutation prevalence reported here is lower than that in a recent pooled analysis of past clinical trials, which reported an overall prevalence of 55.5% (95% CI: 53.9–57.9%) (Peeters M, et al. Eur J Cancer 2015;51:1704–13). Further investigations are required to explain the disparity in these findings.

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