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).
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.
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.
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.
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.
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).
Here we investigated associations between allelic variants of EGFR, ABCG2, and the transporter protein ABCB1 with diarrhea and skin toxicity in gefitinib-treated patients.
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.
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.
Overall response rate gain was achieved up to 10% in patients with wild-type LIFR rs3729740 patients either with wild-type KRAS or skin toxicity (P=0.001) respectively.
The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or Irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS status.
Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy.
In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively.
It is important to recognize that this association, unlike most other BRAF inhibitor-related skin toxicities, can occur many months after commencement of therapy and that vemurafenib treatment can be continued without clinically significant adverse effects.
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.
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.
Combined therapy with BRAF and MEK inhibition improves response rate, progression free survival and overall survival compared with single agent BRAF inhibition, and reduces the skin toxicity that is seen with BRAF inhibitor monotherapy.
The mechanism in which ibrutinib can cause skin toxicities has been thought due to the inhibition of epidermal growth factor; c-Kit and platelet-derived growth factor receptor).