Abstract 4903: Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients
Authors: Park Jin Hyun , Kim Mi Young , Choi In Sil , Kim Ji-Won , Kim Jin Won , Lee Keun-Wook , Kim Jin-Soo 
Published: August 2019

Background: Skin rash is well known predictive marker of response to cetuximab (Cmab) in metastatic colorectal cancer (mCRC). But mechanism of skin rash development is not well understood. After EGFR targeted therapies, the association of the IL-8 level changes and the skin rash has been suggested. The aim of this study was to evaluate the association between skin rash and inflammatory cytokine levels.

Material and Methods: Between 2014 and 2017, we prospectively enrolled a total of thirty-eight mCRC patients treated with chemotherapy with either Cmab or bevacizumab (Bmab) at two hospitals. We performed multiplex cytokine ELISA including twenty inflammatory cytokines including E-selectin, GM-CSF, IFN-alpha, INF-gamma, IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, P-selectin, sICAM-1, and TNF-alpha at baseline before cycle 1, 24 hours after cycle 1, before cycle 2 (=14days), and before cycle 3 (=28days). The cytokine levels were compared by ANOVA test after log-transformation.

Results: Depending on the RAS mutational status,thirty and eight patients were treated with Cmab and Bmab-based chemotherapy, respectively. Of thirty patients who received Cmab plus FOLFIRI, skin rash developed in twenty-three patients (76.6%) after the cycle 1. The mean baseline levels of three groups were described in Table. Only IL-8 levels were significantly different: the mean baseline level of IL-8 in patients with skin toxicity was lower (2.84 ± 0.72) than in patients who did not experienced skin toxicity (3.62 ± 0.51) and received Bmab (3.1 ± 0.8) (ANOVA test, p=0.047).

Skin toxicity(n=23)No skin toxicity(n=7)Bmab(n=8)ANOVA p-valueIL-82.84 ± 0.723.62 ± 0.513.1 ± 0.80.047E-selectin9.94 ± 0.559.89 ± 0.399.91 ± 0.540.968GM-CSF3.95 ± 0.954.17 ± 0.533.63 ± 1.360.597IFN-alpha1.38 ± 0.721.55 ± 0.371.42 ± 0.690.846INF-gamma4.13 ± 1.464.55 ± 1.14.48 ± 1.330.701IL-1 alpha2.37 ± 0.552.69 ± 0.412.26 ± 0.720.310IL-1 beta2.06 ± 1.12.33 ± 0.532.22 ± 1.050.803IL-101.83 ± 0.932.24 ± 0.791.66 ± 0.990.465IL-12p703.66 ± 0.793.84 ± 0.593.79 ± 0.690.812IL-132.07 ± 0.812.26 ± 0.222.08 ± 0.450.808IL-17A3.04 ± 0.853.33 ± 0.533.27 ± 0.780.613IL-44.32 ± 1.114.66 ± 0.724.43 ± 0.920.749IL-64.01 ± 14.17 ± 0.543.84 ± 0.830.782IP-105.19 ± 1.785.76 ± 1.085.71 ± 1.330.601MCP-13.8 ± 0.994.55 ± 0.393.95 ± 0.660.146MIP-1 alpha2.04 ± 0.512.25 ± 0.252.22 ± 0.650.510MIP-1 beta4.78 ± 0.555.02 ± 0.364.65 ± 0.570.387P-selectin9.89 ± 0.659.8 ± 0.699.91 ± 0.490.936sICAM-111.99 ± 0.8612.15 ± 0.912.39 ± 0.850.527TNF-alpha3.97 ± 0.574.18 ± 0.284.05 ± 0.650.670

Conclusion: This study suggests that the inflammatory cytokines levels might be affected by Cmab exposure and associated with the development of skin rash in metastatic CRC patients. The skin rash was related to lower baseline level of IL-8. Further studies are warranted to evaluate this interaction in patients who treated with Cmab.

Citation Format: Jin Hyun Park, Mi Young Kim, In Sil Choi, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Jin-Soo Kim. Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4903.