Thursday, 4 July - Key studies of the day


O-011 - Randomized phase II trial of chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: CAO/ARO/AIO-12 - Hofheinz et al – 

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.

O-007 - ZEBRA: An ACCRU/IRCI multicenter phase II study of pembrolizumab in patients with advanced small bowel adenocarcinoma (SBA) - Pedersen et al - 

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.

O-008 - Proof of concept of the abscopal effect in MSS GI cancers: A phase 2 study of ipilimumab and nivolumab with radiation in metastatic pancreatic and colorectal adenocarcinoma - Parikh et al - 

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.

O-009 - Landscape of FMS-like tyrosine kinase 3 (FLT3) and associated molecular alterations in 44,766 gastrointestinal (GI) cancers – Puccini et al - 

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.

LBA-003 - A phase III study of TAS-118 plus oxaliplatin versus S-1 plus cisplatin as first-line chemotherapy in patients with advanced gastric cancer (SOLAR study) – Kang et al - 

TAS-118 plus oxaliplatin improved survival compared to SP in pts with AGC. Non-hematological toxicities of TAS-118 plus oxaliplatin were greater but manageable. TAS-118 plus oxaliplatin can be a new standard first-line chemotherapy for AGC.