McGovern Medical School, Houston, USA.
Baylor College of Medicine, Houston, USA.
Support Care Cancer. 2022 Oct;30(10):8051-8058. doi: 10.1007/s00520-022-07257-2. Epub 2022 Jun 30.
Epidermal growth factor receptor inhibitors (EGFRI) can be used with pathway inhibitors, including mitogen-activated protein kinase kinase inhibitors (MEKIs), BRAF inhibitors (BRAFIs), and checkpoint inhibitors such as programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) to treat colorectal cancer. These can precipitate treatment-resistant acneiform eruptions, prompting dose modification or discontinuation. Predicting the likelihood of severe rash development and crafting effective treatments may promote adherence to life-saving chemotherapy.
An Institutional Review Board-approved retrospective chart review of patients with colorectal cancer treated with EGFRI or MEKI in combination with HER2, BRAF, PI3K, or checkpoint inhibitors between January 1, 2016, and January 1, 2020, was performed. Surrogates for rash severity were investigated, including lower extremity involvement, utilization of oral steroids or retinoids, dose modification, and incidence of superinfection.
Of 122 patients treated with combination therapy, 105 developed a rash, and 87 developed an acneiform eruption. Common combinations included MEKI/PD-LI, EGFRI/MEKI, and MEKI/PD-1I. Patients treated with EGFRI/MEKI developed the most severe rashes (p = 0.02). Lower extremity involvement was more frequent with EGFRI/MEKI compared to alternative combinations (p = 0.05). Drug holiday correlated with all rash severity surrogates, including rash grade, lower extremity involvement, oral steroid or retinoid use, and incidence of superinfection. Use of oral steroids or retinoids was associated with development of superinfection (p = 0.002). Prophylactic tetracycline use did not impact rash severity or rash incidence.
This is the first descriptive analysis to characterize acneiform eruptions for patients with colorectal cancer on combination cancer therapy. Approximately 85% of patients developed a cutaneous toxicity with what appears to be synergistic effects of EGFRI and MEKI combination therapy causing the most severe eruptions. Superinfection rate correlated to systemic therapy use beyond oral tetracyclines. Further investigation into the utility of prophylactic oral tetracyclines in this population is needed.
表皮生长因子受体抑制剂（EGFRI）可与包括丝裂原活化蛋白激酶激酶抑制剂（MEKI）、BRAF 抑制剂（BRAFIs）和程序性死亡配体 1（PD-L1）和程序性死亡蛋白 1（PD-1）在内的通路抑制剂联合用于治疗结直肠癌。这些药物可能会引发治疗抵抗性痤疮样疹，促使调整剂量或停药。预测严重皮疹发生的可能性并制定有效的治疗方法可能有助于提高对救命化疗的依从性。
对 2016 年 1 月 1 日至 2020 年 1 月 1 日期间接受 EGFRI 或 MEKI 联合 HER2、BRAF、PI3K 或检查点抑制剂治疗的结直肠癌患者进行机构审查委员会批准的回顾性图表审查。研究了皮疹严重程度的替代指标，包括下肢受累、口服类固醇或维甲酸的使用、剂量调整和继发感染的发生率。
在接受联合治疗的 122 名患者中，105 名出现皮疹，87 名出现痤疮样疹。常见的联合治疗包括 MEKI/PD-LI、EGFRI/MEKI 和 MEKI/PD-1I。接受 EGFRI/MEKI 治疗的患者出现最严重的皮疹（p=0.02）。与其他组合相比，EGFRI/MEKI 治疗的患者下肢受累更频繁（p=0.05）。药物假期与所有皮疹严重程度的替代指标相关，包括皮疹分级、下肢受累、口服类固醇或维甲酸的使用以及继发感染的发生率。口服类固醇或维甲酸的使用与继发感染的发生相关（p=0.002）。预防性使用四环素并不影响皮疹严重程度或皮疹发生率。
这是第一项描述性分析，用于描述接受结直肠癌联合癌症治疗的患者的痤疮样疹。大约 85%的患者出现皮肤毒性，EGFRI 和 MEKI 联合治疗似乎具有协同作用，导致最严重的皮疹。继发感染率与除口服四环素以外的全身治疗使用相关。需要进一步研究在该人群中预防性口服四环素的效用。
