The skin types closely related to development of the facial acneiform rash and the therapeutic effects of EGFR inhibitors in RAS wild-type metastatic colorectal cancer: Ancillary analysis of FAEISS study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3637-3637
Author(s):  
Syusuke Yoshikawa ◽  
Naoya Yamazaki ◽  
Yoshio Kiyohara ◽  
Keiko Nozawa ◽  
Haruhiko Fukuda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Topical Corticosteroid ◽  
Metastatic Colorectal Cancer ◽  
Egfr Inhibitors ◽  
Therapeutic Effects ◽  
Egfr Inhibitor ◽  
Wild Type ◽  
Primary Disease ◽  
Acneiform Rash ◽  
Pre Treatment

3637 Background: At ESMO2019, we reported the primary results of a randomized controlled trial (FAEISS study) investigating the efficacy of topical corticosteroid treatment to facial acneiform rash (AR) by EGFR inhibitors comparing groups starting with a very strong topical corticosteroid and the standard weak topical corticosteroid. As an ancillary analysis, we investigated the association between AR and the pre-treatment skin types, as well as between the skin types and therapeutic effects of EGFR inhibitors on the primary disease. Methods: Utilizing pre-treatment clinical photos of the face taken according to the method determined by FAEISS study protocol, we divided the skin types into categories including enlarged pore, oiliness, xerosis, wrinkles, skin color/redness, and allocated the score (1-3) by central review. The severity of AR occurred during the study was graded and was evaluated the association with the specific skin type by Fisher’s exact test. We also investigated the association between the skin types and the best overall response (RECISTv1.1) to EGFR inhibitor therapy on the primary disease using the Cochran-Armitage trend test. Results: Of the registered 172 cases of RAS wild-type metastatic colorectal cancer [104 men and 68 women, median age = 68 (26-79)], omitting the cases with unevaluable data, finally we analyzed 146 cases for associations between the skin types and AR and 147 cases for best overall response. Interestingly, AR developed 13.6% of enlarged pore score 1, 29% of score 2 and 45.8% of score 3, and patients with enlarged pore tended to have more AR (p = 0.058). Surprisingly, the response(CR/PR/SD) of the primary disease were 59.1% of the enlarged pore score 1, 70.6% of score 2 and 87.0% of score 3, and showed statistically significant trend(p < 0.038). Conclusions: This study suggested that a skin type (enlarged pore) is a possible marker predicting AR risk in EGFR inhibitor therapy for RAS wild-type metastatic colorectal cancer, and better therapeutic effects of EGFR inhibitors.

scholarly journals Right vs left-sided RAS wild-type metastatic colorectal cancer treated with EGFR inhibitors: prognostic differences

2019 ◽  
Vol 30 ◽  
pp. iv53
Author(s):  
S. Duarte ◽  
I. Grilo ◽  
K. Ladeira ◽  
J. Pimenta ◽  
P. Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Egfr Inhibitors ◽  
Wild Type

scholarly journals Phase II study of tivantinib (ARQ 197) and cetuximab in patients with EGFR inhibitor-resistant, MET-High, KRAS wild-type (KRASwt) metastatic colorectal cancer (mCRC)

2017 ◽  
Vol 28 ◽  
pp. iii11 ◽  
Author(s):  
Lorenza Rimassa ◽  
Silvia Bozzarelli ◽  
Stefano Cordio ◽  
Filippo Pietrantonio ◽  
Laura Toppo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Egfr Inhibitor ◽  
Wild Type ◽  
Arq 197

scholarly journals Circulating Methylated DNA to Monitor the Dynamics of RAS Mutation Clearance in Plasma from Metastatic Colorectal Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3633
Author(s):  
Chiara Nicolazzo ◽  
Ludovic Barault ◽  
Salvatore Caponnetto ◽  
Marco Macagno ◽  
Gianluigi De Renzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Wild Type ◽  
Gene Methylation ◽  
Ras Mutation ◽  
First Line Therapy ◽  
Ras Status ◽  
Pre Treatment ◽  
Ctdna Analysis

The clearance of RAS mutations in plasma circulating tumor DNA (ctDNA) from originally RAS-mutant metastatic colorectal cancer (mCRC) has been recently demonstrated. Clinical trials investigating whether RAS mutant mCRC who “convert” to wild-type in plasma might benefit from EGFR blockade are ongoing. Detection of tumor-specific DNA methylation alterations in ctDNA has been suggested as a specific tool to confirm the tumoral origin of cell-free DNA. We monitored RAS clearance in plasma from patients with RAS-mutant mCRC at baseline (pre-treatment) (T0); after 4 months of first-line therapy (T1); at the time of first (T2) and second (T3) progression. A five-gene methylation panel was used to confirm the presence of ctDNA in samples in which RAS mutation clearance was detected. At T1, ctDNA analysis revealed wild-type RAS status in 83% of samples, all not methylated, suggesting at this time point the lack of ctDNA shedding. At T2, ctDNA analysis revealed wild-type RAS status in 83% of samples, of which 62.5% were found methylated. At T3, 50% of wild-type RAS samples were found methylated. Non-methylated samples were found in patients with lung or brain metastases. This five-gene methylation test might be useful to confirm the presence of ctDNA in RAS wild-type plasma samples.

miRNA expression as a predictor of survival in patients with metastatic colorectal cancer treated with EGFR inhibitors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14059-e14059
Author(s):  
Sandrine Imbeaud ◽  
Gilles Manceau ◽  
Jean-Baptiste Bachet ◽  
Jean-François Emile ◽  
Frédéric Bibeau ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prediction Model ◽  
Metastatic Colorectal Cancer ◽  
Mirna Expression ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards Model ◽  
Egfr Inhibitors ◽  
Wild Type ◽  
Mirna Profiling ◽  
Disease Free

e14059 Background: The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. EGFR inhibitors have been tested for treatment of a variety of cancers but they are generally plagued by low response rates, leading to ineffective or non-optimal chemotherapy, unnecessary drug toxicity and expense. In colorectal cancer, KRAS mutations are clearly associated with resistance to anti-EGFR antibodies. A major challenge is to identify, in non-mutated KRAS patients, markers that can predict response to this therapy. This study aimed to develop a miRNA expression-based model for evaluating the responsiveness of patients with KRAS wild-type metastatic colorectal cancer to one or more EGFR inhibitors prior to treatment. Methods: miRNA profiling of KRAS wild-type tumors was performed on a discovery set of 44 patients with metastatic colorectal cancer treated with anti-EGFR inhibitors. A miRNA expression-based predictor of survival risk group was calculated by combining a Cox proportional hazards model and a supervised principal component method. Results: miRNA profiling of the discovery set identified hsa-miRNA-31* whose expression in tumor samples was highly correlated with survival and displayed prediction prospective for disease-free and overall survivals. Parameters of the hsa-miRNA-31* expression-based prediction model were determined on a subgroup of 23 patients. Its discriminative ability was evaluated on the complementary 21 samples that included 19 events. In this validation set, 4 of the 6 patients classified as “low risk” by the model survived for more than 25 weeks as disease-free whereas 11 of the 13 patients classified as “high risk” displayed disease progression within 25 weeks, suggesting a specificity of 85% [95% CI: 54%-98%] and a sensitivity of 67% [95% CI: 22%-96%] for the prediction model. These values were associated with a PPV of 67%, [95% CI: 22%-95%] and a NPV of 85% [95% CI: 54%-98%]. Conclusions: Our findings demonstrated that a prediction model based on the level of expression of hsa-miRNA-31* could evaluate whether a patient with a KRAS wild-type metastatic colorectal cancer is likely to respond to an EGFR inhibitor.

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