Analysis of skin toxicity as a function of EGFR intron 1 polymorphism showed a tendency for higher toxicity in patients with a low number of CA-repeats (p = 0.058).
However, trends for increased gastrointestinal and skin toxicity were observed with greater phosphorylation or quantities of EGFR, ERK, and AKT in tumor samples (P </= .05).
In 126 patients with cancer and EGFR inhibitor therapy skin toxicity was quantified and EGFR and inflammatory pathway genes were analyzed by deep sequencing.
The mechanism through which skin toxicity arises during treatment with EGFR inhibitors is not well known, but seems to be due to the modification of the RAS/RAF/MEK/ERK signal path associated with its activation, which results in the similarity between the adverse effects of EGFR inhibitors and the treatment of melanoma with BRAF and MEK inhibitors.
Although skin toxicities are the most common adverse events associated with EGFR inhibitors, the differences in efficacy and safety between pre-emptive and reactive skin treatment according to KRAS tumor status has not been reported.
These results suggest that the EGFR D994D polymorphism is a useful biomarker for predicting the severity of skin toxicity in patients receiving antibody against EGFR.
We acquired Raman spectra of skin of patients undergoing treatment with MEK, EGFR, or BRAF inhibitors, which are known to induce severe skin toxicity; for this pilot study, three patients were included for each inhibitor.
Our study revealed an influence of the EGFR-R521K genotype on skin toxicity and suggested its relation to clinical activity of cetuximab/docetaxel treatment.
Sex (p=0.005), non-smoking status (p=0.010), skin toxicity (p=0.020), EGFR gene mutations (p<0.001) and EGFR FISH positivity (p=0.016) were found to be associated with gefitinib response.
A placebo-controlled phase 3 trial demonstrated that the epidermal growth factor receptor (EGFR) inhibitor erlotinib in combination with gemcitabine was especially efficient in a pancreatic ductal adenocarcinoma (PDAC) subgroup of patients developing skin toxicity.
Here, we present the first genome-wide association study (GWAS) to find single nucleotide polymorphisms (SNPs) associated with EGFR inhibitor-induced skin toxicity using data of the multicentre randomized phase III CAIRO2 trial (clinicaltrials.gov NCT00208546).
The results suggest that EGFR-TKIs significantly increase the risk of skin toxicities including all-grade rash, pruritus, dry skin, and high-grade rash, pruritus.
These results suggest that polymorphic variations in the intron 1 of the egfr gene is associated with response to EGFR inhibitors and may provide an explanation as to why the development of skin toxicity is associated with a favorable outcome in patients treated with these agents.
The biology of responsiveness is still unclear, although there is growing evidence of an association of skin toxicity or presence of shorter EGFR intron 1 cytosine-adenine repeats with positive outcome.
This pilot study provides preliminary evidence supporting genetic variation of EGFR (rs2227983), KRAS (rs61764370) and FCGR2A (rs180127) as useful biomarkers for predicting reduced skin toxicity in HNSCC patients treated with a cetuximab-based therapy.
Clinically managing skin toxicity associated with anti-EGFR antibody usage to treat colorectal cancer improves quality of life for colorectal cancer patients.