Results of the non-small cell lung cancer part of a phase III, open-label, randomized trial evaluating topical corticosteroid therapy for facial acneiform dermatitis induced by EGFR inhibitors: stepwise rank down from potent corticosteroid (FAEISS study, NCCH-1512)

Kazumi Nishino,Yuichiro Ohe,Ryota Saito,Haruhiko Fukuda,Katsuko Kikuchi,Naoya Yamazaki,Tetsuya Hamaguchi,Yasuo Nakai,Tetsu Kobayashi,Yoshio Kiyohara,Taro Shibata,Eisaku Miyauchi,Keiko Nozawa,Toshiaki Takahashi,Yutaka Fujiwara

doi:10.1007/s00520-020-05765-7

Abstract

PurposeThis FAEISS study was designed to confirm the superior efficacy of reactive topical corticosteroid strategies employing serially ranking-DOWN from very strong steroid levels for the treatment of facial acneiform rash induced by epidermal growth factor receptor (EGFR) inhibitors (EGFRIs), in comparison with strategies employing serially ranking-UP from weak steroid levels. This article reports the primary results of the non-small cell lung cancer (NSCLC) part of the trial.MethodsPatients with EGFR-mutated advanced NSCLC treated with erlotinib or afatinib were enrolled in the first registration. All patients received preemptive therapy with oral minocycline and heparinoid moisturizer from the initiation of an EGFR inhibitor. Enrolled patients who developed facial acneiform rash within 2 weeks were randomized at second registration to either a ranking-UP (WEAK) group or a ranking-DOWN group. The primary endpoint was incidence of grade ≥ 2 facial acneiform rash over 8 weeks.ResultsFifty-one patients were enrolled at the first registration and received EGFRIs (n = 30 for afatinib, n = 21 for erlotinib). However, 35 patients did not develop facial acneiform rash within 2 weeks; one patient discontinued preemptive treatment. Fifteen patients (29.4%) were enrolled in the second registration; nine were assigned to the WEAK group and six to the DOWN group. There was no significant difference in the incidence of grade ≥ 2 facial acneiform rash between the WEAK group (one patient, twice) and the DOWN group (one patient, twice; p = 0.8417). No patients developed severe facial acneiform rash within 10 weeks.ConclusionIn NSCLC patients who received EGFRIs, preemptive therapy of oral minocycline and heparinoid moisturizer reduced facial acneiform rash incidence.Trial registrationUMIN000024113

Highlights

Epidermal growth factor receptor (EGFR) inhibition is an established and effective treatment option for patients withExtended author information available on the last page of the article non-small cell lung cancer (NSCLC) [1,2,3,4], colorectal cancer (CRC) [5, 6], and squamous cell carcinoma of the head and neck (SCCHN) [7]
Eligible patients were EGFR-mutant NSCLC patients who were to be treated with erlotinib or afatinib, and wild-type KRAS and NRAS patients with metastatic CRC who were to be treated with cetuximab or panitumumab
A key secondary endpoint, the incidence of adverse events on the face, is clearly assumed not to exceed in the WEAK group compared with that in the DOWN group. If these two endpoints are met, we may conclude that reactive treatment starting with very strong topical corticosteroids is more effective against facial acneiform rash

Summary

Introduction

Epidermal growth factor receptor (EGFR) inhibition is an established and effective treatment option for patients withExtended author information available on the last page of the article non-small cell lung cancer (NSCLC) [1,2,3,4], colorectal cancer (CRC) [5, 6], and squamous cell carcinoma of the head and neck (SCCHN) [7]. The incidence of facial acneiform rash of all grades has been estimated to be 60–90% from previous clinical trials [11, 12] These adverse reactions are rarely serious or life-threatening, skin toxicity can significantly affect quality of life (QOL), causing both physical discomfort and psychological distress, which can affect compliance, affecting the efficacy of treatment with EGFR inhibitors [13,14,15,16]. Lacouture et al reported that preemptive treatment, including skin moisturizers, sunscreen, topical steroid, and doxycycline, could reduce the severity of EGFR inhibitor-associated skin toxicities in patients with metastatic CRC [17]. Since EGFR-TKIs induce less skin toxicity than EGFR antibodies, patients with NSCLC harboring EGFR mutations are generally treated only with preventative moisturizers, and with reactive oral minocycline and topical steroids only at the onset of the rash

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Results

Conclusion