Thursday, 4 July - Key studies of the day
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Upfront CRT followed by consolidation CT was feasible, resulted in better compliance to CRT but worse compliance to CT compared to group A. Long term follow-up is required to assess if improved pCR in arm B translate to better oncological outcome.
In the largest study of SBA to date, and the first using immunotherapy, Pembrolizumab did not achieve the goal ORR in pretreated advanced SBA pts; however, it may control disease in some MSS patients (1 PR, DCR 50%), though further study is needed to confirm this outcome. Efficacy in MSI-H is confirmed. Further predictive marker testing is underway.
Dual blockade of CTLA-4 and PD-1 with RT is feasible and demonstrates promising activity in patients with advanced MSS CRC and PDAC. Updated efficacy data and outcomes from correlative serial biopsies will be reported subsequently.
FLT3amp co-occurs with KRAS mutations at a frequency similar to the overall CRC population, unlike HER2amp CRC which has a lower frequency of KRAS co-mutation and is thought to activate downstream signaling pathways (PMID: 29338072). In contrast, both FLT3amp and HER2amp CRC are enriched for TP53 mutations. The distinct genomic landscape of FLT3amp relative to HER2amp CRC combined with the response of FLT3amp index cases may suggest FLT3amp has a distinct oncogenic role for colon cancer that extends beyond signaling activation only. Further investigation of the oncogenic role of FLT3amp is needed in a clinical context and an appropriate model system.