Incidence and potential prognostic implications of fibroblast growth factor receptor gene alterations and coexisting mutations in colorectal cancer.

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e15558 Background: The fibroblast growth factor receptor (FGFR) family comprises four tyrosine kinase receptors (FGFR1-4). FGFR1 amplification (6.3%) as well as overexpression of FGFR1 (10.1%), FGFR2 (5.5%) and FGFR3 (16.2%) have been demonstrated in primary colorectal cancer (CRC, incidence in brackets). The prognostic utility of testing FGFR alterations and association with response to FGFR-inhibitors are still emerging. Here, we report FGFR alteration data with clinicopathological correlations and survival outcomes from a Sydney based Local Health District in Australia. Methods: Clinicopathological data was analysed from 341 ethnically diverse patients with CRC treated at Southwestern Sydney Local Health District from 2014-2021. Next generation sequencing for point mutations, deletions, and amplifications was performed using the Qiagen 30-gene panel. Mismatch repair (MMR) status was determined using immunohistochemical staining. Demographic characteristics, histological features and survival outcomes were recorded from electronic medical records. Results: Of the 341 patients, 42 (12.3%) had FGFR alterations of which 52% were men and 48% women. 32 patients were Caucasian, 4 Middle Eastern, 5 Asian and 1 South American. Median age at diagnosis was 66 years. Of the 42 patients, FGFR1 mutations were present in 26.2%, FGFR1 amplifications in 4.7% and FGFR1 deletions in 4.7%. FGFR2 mutations were present in 16.7%, and 50% had FGFR3 mutations. One patient had concurrent FGFR1 and FGFR3 mutations. The vast majority were adenocarcinoma (81%), followed by mucinous adenocarcinoma (17%) and adenocarcinoma with neuroendocrine features (2%). 21.4% of patients with FGFR alterations had concurrent KRAS mutations, 28.6% had concurrent BRAF mutations (91.6% V600E) and MMR-deficiency was present in 19%. Median overall survival of patients with FGFR alterations was 44 months, for those who also had deficient MMR 48 months, concurrent BRAF V600E mutations 51 months and concurrent KRAS mutations 71 months. 43% (18 patients) were stage 4 at presentation. Of these 18 patients, 7 had FGFR1 mutations, 1 had a FGFR2 mutation and 10 had FGFR3 mutations. The median overall survival of patients with stage 4 disease was 11 months and those with concurrent BRAF V600E mutations 17 months. Two patients had concurrent KRAS mutations (both G12V), with median overall survival of 5.5 months and 1 patient had MMR deficiency, with an overall survival of 9 months. Conclusions: FGFR alterations were identified in 12.3% of patients with colorectal cancer in an ethnically diverse cohort in Australia. Concurrent KRAS and BRAF mutations appear to affect survival outcomes. Further multivariate analyses are underway.