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Published on: August 11, 2017
Clinical research of EGFR inhibitors and related dermatologic toxicities
Roman Perez-Soler1, Eric Van Cutsem
1Division of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA. rperezso@montefiore.org
Abstract:
An acneiform-like skin toxicity is commonly observed in patients with solid tumors treated with epidermal growth factor receptor inhibitors (EGFRIs). This symptomatic rash is related to epidermal growth factor receptor (EGFR) inhibition in the skin. A positive relation between the presence and severity of treatment-related rash and survival has been consistently observed with all EGFRIs approved for clinical use. These findings suggest that rash may be a useful surrogate marker of successful EGFR inhibition and clinical benefit and therefore of possible use in identifying patients most likely to benefit from therapy, as well as to guide dose adjustments. Increasing drug dose until skin toxicity appears is being studied. Further studies are needed to thoroughly evaluate the value of skin toxicity as a surrogate marker for clinical benefit. Current treatments of the skin toxicity are empirical and oriented toward mitigating symptoms and not validated by well-controlled clinical trials. Rational treatments based on the biological mechanisms of the skin toxicity must be developed and tested in well-controlled clinical trials.
Insights
Skin rash from epidermal growth factor receptor inhibitors (EGFRIs) may indicate better survival in cancer patients. Further research is needed to confirm rash as a reliable marker for treatment effectiveness and guide therapy.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Acneiform-like skin toxicity is a frequent side effect of epidermal growth factor receptor inhibitors (EGFRIs) used in solid tumor treatment.
- This rash is a direct consequence of EGFR inhibition within the skin.
- A correlation between rash severity and improved patient survival has been noted across various EGFRIs.
Purpose of the Study:
- To explore the potential of treatment-related rash as a surrogate marker for EGFR inhibition efficacy.
- To investigate the utility of rash in patient selection and dose adjustment strategies for EGFRIs.
- To highlight the need for evidence-based treatments for EGFRI-induced skin toxicity.
Main Methods:
- Observational analysis of clinical data from patients treated with EGFRIs.
- Correlation studies assessing the relationship between rash presence/severity and survival outcomes.
- Review of current treatment approaches for EGFRI-related skin toxicity.
Main Results:
- Consistent positive association observed between EGFRI-induced rash and enhanced patient survival.
- Rash severity may serve as an indicator of successful EGFR inhibition and clinical benefit.
- Current symptomatic treatments for skin toxicity lack robust clinical validation.
Conclusions:
- EGFR-inhibitor-related rash shows promise as a surrogate marker for treatment efficacy and clinical benefit.
- Further investigation is warranted to validate rash as a predictive biomarker for guiding EGFRI therapy and dose adjustments.
- Development and testing of mechanism-based treatments for EGFRI-induced skin toxicity are crucial.
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