FOCUS 3: A study to determine the feasibility of molecular selection of therapy using K-RAS, B-RAF, and topo-1 in patients with advanced colorectal cancer (ACRC).
Maughan T., Wilson RH., Williams GT., Seymour MT., Richman SD., Quirke P., Pope J., Pope M., Parmar M., Nelson A., Meade AM., Nichols LL., Jasani B., Hodgkinson E., Fisher D., Butler R., Bridgewater JA., Adams RA., Kaplan RS.
563 Background: Molecular characteristics of cancer vary between individuals. In future increasing numbers of trials will require assessment of biomarkers in order to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The FOCUS 3 trial is a feasibility study to assess whether tumour samples could be collected from referring hospitals' pathology departments, sent to designated reference laboratories for biomarker evaluation, and results provided to oncologists within 10 working days. METHODS: Patients with ACRC, fit for chemotherapy, were registered from 24 centres between 02.10 and 04.11. Following consent, paraffin embedded tumour samples were sent to Cardiff or Leeds for analysis of topoisomerase 1 (topo-1) by immunohistochemistry and of KRAS and BRAF mutation status, and results were forwarded to the MRC CTU. Patients were classified into 1 of 4 molecular strata, which determined the set of 2 hypothesis driven experimental therapies they could be randomised to in addition to control chemotherapy (irinotecan + 5FU). At this stage eligibility was reconfirmed and consent for randomisation obtained. RESULTS: 332 patients were registered to participate in FOCUS 3. Biomarker results were provided to oncologists within 10 working days (wd) in 71%, within 15 wd in 91% and within 20 wd in 99% patients. A 4 stage suite of patient information sheets (PIS) was designed and implemented to avoid patient overload; separate information sheets were provided to patients at stages during the consent process and patient understanding was assessed. 93% of eligible patients gave consent to randomisation. KRAS mutation was detected in 88 (36%), BRAF in 15 (6%), 2 patients had both mutations and 133 were double wildtype. 77% of patients were high (2-3), 19% low (0-1) and 4% inconclusive for topo-1. Tumour response and toxicity results for the 244 randomised patients will be presented. CONCLUSIONS: Patient samples can be collected and analysed at designated reference laboratories within acceptable timeframes. Multi-arm designs can be made acceptable to patients through good PIS, ensured by patient and carer input into their design.