research on the treatment for mcc

1. RESPONSE OF EGFR AGENTS IN COMBINATION WITH CHEMOTHERAPY
DEMONSTARTED INPATIENS WITH METASTATIC COLORECTAL CANCER
OF RARE KRAS MOLECULAR SUBTYPE
Aim:
To determine whether cetuximab in combination with
chemotherapeutic drugs could be effective in case of mCRC with KRAS
gene mutation.
Definitions:
EGFR – Epidermal growth factor receptors
 These receptors are normally found in cell surface and are
activated by TGF-alpha and EGF.
 When activated, it results in auto phosphorylation of tyrosine and
thereby signaling several proteins.
 These proteins are necessary for the cell migration, cell
proliferation and adhesion.
Mutation in EGFR:
 Mutation in EGFR may leads to over expression of EGFR, which in
turn leads to the increased cell proliferation, increased cell
migration and increased adhesion.
 This in turn leads to tumor formation and inflammation.
KRAS:
 This is a protein in human encoded by KRAS gene
 KRAS acts as a molecular on/off switch.
 Once it is turned on, it recruits and activates proteins necessary
for the propagation of growth factor and other receptors' signal
such as c-Raf and PI 3-kinase.

2. EGFR inhibitors:
These drugs binds to EGFR and prevents it to activate.
Methods:
Cetuximab on mCRC
 Two clinical trials were made to analysis the effectiveness of
cetuximab on mCRC.
 OPUS and CRYSTAL were those two trials.
 OPUS is trails using Cetuximab in combination with FOLFOX-4
(Fluorouracil, Leucovorin and oxaleplatin)
 CRYSTAL is the trail using Cetuximab with FOLFIRI (fluorouracil,
Leucovorin and irinotecan)
 These two trails provide evidence that cetuximab has shown
response to treatment and reduce disease progression and
cetuximab has no effect when KRAS gene is mutated.
AGITG ICECREAM trial
 AGITG – Australian Gastro Intestinal Trial Groups
 ICECREAM – Irinotecan Cetuximab Evaluation and Cetuximab
Response Evaluation Among patients with G13D Mutation
 2 Aim of this trials
o To determine whether cetuximab is used as monotherapy or
in combination with Irinotecan based regimen in KRAS WT
patients.
o To determine whether efficacy of either cetuximab alone or
in combination is similar harboring in KRAS G13D mutation.
 Results
After 6 months of clinical trial

3. o PFS rates of 10% in cetuximab arm when compared to 23%
in irinotecan-cetuximab combination arm. Median time of
progression is similar 2.5 months vs 2.6 months
o Cetuximab monotherapy showed no partial response, stable
disease at 58% of patients but in irinotecan – cetuximab
combination 9% partial response and 70% stable disease
was determined.
CONCLUSION:
From the clinical trial conducted by AGITG, it has been clear that
cetuximab combination with chemotherapeutic drug has response over
mCRC with KRAS gene mutation.