Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2019 Aug;8(9):4169-4175.
doi: 10.1002/cam4.2132. Epub 2019 Jun 14.

Evaluation of EGFR inhibitor-mediated acneiform skin toxicity within the double-blind randomized EVITA trial: A thorough gender-specific analysis using the WoMo score

Maria R Gaiser  1   2 , Sylvie Lorenzen  3 , Kirsten Merx  4 , Jörg Trojan  5 , Janja Ocvirk  6 , Thomas J Ettrich  7 , Salah-Eddin Al-Batran  8 , Holger Schulz  9 , Nils Homann  10 , Hans-Peter Feustel  11 , Michael Schatz  12 , Melanie Kripp  4 , Nadine Schulte  4 , Steffen Heeger  13 , Soetkin Vlassak  14 , Winfried Koch  15 , Ralf-Dieter Hofheinz  4
Affiliations
Clinical Trial

Evaluation of EGFR inhibitor-mediated acneiform skin toxicity within the double-blind randomized EVITA trial: A thorough gender-specific analysis using the WoMo score

Maria R Gaiser et al. Cancer Med. 2019 Aug.

Abstract

Acne-like skin reactions frequently occur in patients undergoing treatment with drugs inhibiting the epidermal growth factor receptor. Recently, the effects of vitamin K1 containing cream (Reconval K1) as prophylactic skin treatment in addition to doxycycline were explored in a double-blind randomized phase II trial (EVITA) in patients with metastatic colorectal cancer receiving cetuximab. EVITA demonstrated a trend towards less severe skin rash in Reconval K1-treated patients using the tripartite WoMo skin reaction grading score as a thorough tool for quantification of drug related skin reactions. This gender-specific analysis of the EVITA trial evaluated the application of the WoMo score for assessment of epidermal growth factor receptor (EGFR)-related skin toxicities according to treatment arm and gender. To show the robustness of results parametric and non-parametric statistical analyses were conducted. All three parts of the WoMo score independently demonstrated the superiority of the treatment arm (Reconval K1) regarding a significant reduction in acneiform skin reactions in women. Men did not benefit from Reconval K1 cream at any time point in none of the WoMo score analyses. The treatment effect in women was confirmed by the use of skin rash categories based on the final WoMo overall score and mixed effect longitudinal multiple linear regression analysis. The WoMo score represents a sensitive tool for studies exploiting treatments against EGFR mediated acne-like skin rash. Part C of the WoMo score seems to be sufficient for quantification of drug related skin toxicities in further studies. Standard WoMo skin reaction score values for future studies are provided.

Keywords: EGFR inhibitor; WoMo score; acneiform skin toxicity; women.

PubMed Disclaimer

Conflict of interest statement

MRG has received honoraria from Roche, MSD, BMS, Merck KGaA, Novartis, Pierre Fabre. S‐E A‐B has an advisory role with Merck, Roche, Celgene, Lilly, Nordic Pharma, Bristol‐Myers Squibb, and MSD Sharp & Dohme; is a speaker for Roche, Celgene, Lilly, Nordic Pharma, AIO gGmbH, MCI, promedicis, and Forum für Medizinische Fortbildung; He is CEO/founder of IKF Klinische Krebsforschung GmbH and has received research grants from Sanofi, Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly, German Cancer Aid (Krebshilfe), German Research Foundation and the Federal Ministry of Education and Research. RDH has received honoraria from Merck KGaA, Amgen, Roche, MSD, BMS, medac, Lilly, Sanofi, Boehringer. He has served as an advisor for Amgen, Merck KGaA, Roche, MSD, BMS, medac, Lilly, Sanofi, Boehringer. His institution has received research funding from Amgen, Merck KGaA, Amgen, Sanofi. All remaining authors have declared no conflict of interest.

Figures

Figure 1
Figure 1
Observed mean values for WoMo C score according to gender (women: left part; men: right part), allocated treatment arm (Vitamin K: dark grey bars, vehicle: light grey bars), and treatment week
Figure 2
Figure 2
(A) Model estimated time course of WoMo C by treatment (women). (B) Model estimated time course of WoMo C by treatment (men)
Figure 3
Figure 3
Evolution of categories of WoMo score according to treatment arm in female patients (A) and male patients (B). Note: Each bar indicates the percentage of patients with values for the respective week. White bars represent patients without rash (zero points), light grey bars indicate mild rash (1‐20 points), dark gray bars indicate moderate rash (21‐40 points), and black bars indicate severe rash (>40 points). The width of bars is proportional to the number of patients evaluated for the corresponding week and treatment
See this image and copyright information in PMC

References

    1. Hofheinz RD, Segaert S, Safont MJ, Demonty G, Prenen H. Management of adverse events during treatment of gastrointestinal cancers with epidermal growth factor inhibitors. Crit Rev Oncol Hematol. 2017;114:102‐113. - PubMed
    1. Lacouture ME, Mitchell EP, Piperdi B, et al. Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open‐label, randomized trial evaluating the impact of a pre‐Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:1351‐1357. - PubMed
    1. Hofheinz RD, Deplanque G, Komatsu Y, et al. Recommendations for the prophylactic management of skin reactions induced by epidermal growth factor receptor inhibitors in patients with solid tumors. Oncologist. 2016;21:1483‐1491. - PMC - PubMed
    1. Kobayashi Y, Komatsu Y, Yuki S, et al. Randomized controlled trial on the skin toxicity of panitumumab in Japanese patients with metastatic colorectal cancer: HGCSG1001 study. J‐STEPP. Future Oncol. 2015;11:617‐627. - PubMed
    1. Hofheinz RD, Lorenzen S, Trojan J, et al. EVITA – A double‐blind, vehicle controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab‐induced skin toxicity. Ann Oncol. 2018;29:1010‐1015. - PubMed

Publication types

MeSH terms