RAS Switch in Patients With Metastatic RAS Native Colorectal Tumors Treated With 1st Line FOLFIRI-Cetuximab
Status:
Unknown status
Trial end date:
2015-12-01
Target enrollment:
Participant gender:
Summary
Adenocarcinoma of the colon and rectum is a common, serious disease and it is the second
cause of death from cancer in Spain.
The prognosis of CRC depends to a great extent on its stage when diagnosed. Patients with
advanced disease, who present up to 40% of all patients, have a poor prognosis. Although the
application of modern chemotherapy and radiotherapy treatments obtains median survival
periods of around 24 months, the proportion of patients with advanced disease who obtain a
cure is low.
Systemic treatment of advanced CRC has changed considerably in the last ten years with the
introduction of active drugs such as oxaliplatin, irinotecan, and capecitabine. The most
commonly used first line regimens are 5-Fluorouracil-Leucovorin-Oxaliplatin (FOLFOX),
Capecitabine-Oxaliplatin (XELOX), 5-Fluorouracil-Leucovorin-Irinotecan (FOLFIRI) and, to a
lesser extent, Capecitabine-Irinotecan (XELIRI). Chemotherapy regimens are combined with
different agents against therapeutic targets, three of which are effective in colon cancer:
bevacizumab, which targets vascular endothelial growth factor (VEGF) and cetuximab or
panitumumab, which target the epidermal growth factor receptor (EGFR).
The use of cetuximab and panitumumab is not recommended in patients with KRAS mutations and
the combination of a VEGF and EGFR agents is not beneficial.
Two recent studies results have identified KRAS mutations as frequent drivers of acquired
resistance to cetuximab and panitumumab in colorectal cancer patients. The conclusions
indicate that the emergence of KRAS mutant clones can be detected non-invasively months
before radiographic progression by a DNA Blood Test (Inostics´BEAMing Technology).
Centro Integral Oncológico Clara Campal (CIOCC) is aiming to undertake a pioneer project
aimed at integrating the analysis of KRAS switch status by BEAMing Technology in patients
with metastatic colorectal cancer, tumor KRAS wild-type and BEAMing wild-type treated with
first line FOLFIRI-cetuximab
In naive chemotherapy tumor-KRAS wild-type metastatic colorectal cancer patients, who are
BEAMing positive (KRAS mutated in blood) before treatment may have worse evolution in terms
of PFS (progression Free Survival) and response rate than BEAMing negative (KRAS native in
blood) patients.
To know the proportion of patients who are BEAMing positive (KRAS mutation can be detected in
circulating extracellular DNA) at the beginning of treatment, could be of great importance
for treatment efficacy.