A Randomized Controlled Trial of Epidermal Growth Factor Ointment for Treating Epidermal Growth Factor Receptor Inhibitor-Induced Skin Toxicities

Abstract

Background: The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs).

Materials and methods: This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily.

Results: Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm.

Conclusion: EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events.

Keywords: Adverse event; Epidermal growth factor ointment; Epidermal growth factor receptor; Quality of life; Skin.

Figure 1

A 63‐year‐old female patient with non‐small cell lung cancer treated with erlotinib (150 mg). (A): Erythematous multiple macules and patches were observed on face, upper extremities, chest, and trunk. (B): Improved skin lesions following 4 weeks of treatment (arm 2; EGF 1 ppm).

Figure 2

Histopathological findings of Figure 1. (A): Dense dermal infiltration of neutrophils and lymphohistiocytes and spongiosis of epidermis with focal pustular scab formation. (B): Markedly reduced inflammatory cell infiltration after 4 weeks of treatment (arm 2; EGF 1 ppm).

Figure 3

A 54‐year‐old female patient with colon cancer treated with cetuximab‐based regimen. (A): Acneiform papules and pustules, and crusts on the face. (B): Improved skin lesions following 4 weeks of treatment (arm 3; EGF 20 ppm).