Dermatology: Practical and Conceptual


Research Letter | Dermatol Pract Concept. 2024;14(4):e2024259 1

Impact of Xerosis in Patients with Cancer Receiving 
Epidermal Growth Factor Receptor  

or Mitogen-Activated Protein Kinase Inhibitors:  
ATIXI, A Non-Interventional Prospective Pilot Study
Pietro Quaglino1, Giuseppe Argenziano2, Emi Dika3,4, Michela Starace4,5, Simone Amabile1, 
Paolo Fava1, Elvira Moscarella2, Bianca Maria Piraccini4,5, Alain Delarue6, Olivia Dialla7, 

Fabienne Zumaglini6, Giampiero Girolomoni8

1 Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy

2 Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi  

Vanvitelli Naples, Italy

3 Oncologic Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy

4 Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy

5 Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy

6 Pierre Fabre, Lavaur, France

7 Pierre Fabre, Boulogne-Billancourt, France

8 Department of Medicine, Section of Dermatology, University of Verona, Italy

Key words: Adverse effects, Anti-cancer treatments, Cutaneous toxicity, EGFR inhibitors, MEK inhibitors, Xerosis

Citation: Quaglino P, Argenziano G, Dika E, et al. Impact of Xerosis in Patients With Cancer Receiving Epidermal Growth Factor 
Receptor or Mitogen-Activated Protein Kinase Inhibitors: ATIXI, A Non-Interventional, Prospective, Pilot Study. Dermatol Pract Concept. 
2024;14(4):e2024259. DOI: https://doi.org/10.5826/dpc.1404a259

Accepted: May 28, 2024; Published: October 2024

Copyright: ©2024 Quaglino et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, 
distribution, and reproduction in any medium, provided the original authors and source are credited.

Funding: This study and its related cost and fees, medical writing assistance for the preparation of this manuscript and the open access 
publishing fees were supported by Pierre Fabre.

Competing Interests: PQ has received advisory board and speaker fees from Novartis and Pierre-Fabre. AD, OD and FZ are employees of 
Pierre Fabre. GA, ED, MS, SA, PF, EM, BMP have no conflicts of interest to declare. GG has received personal fees from AbbVie, Almirall, 
Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli-Lilly, Leo Pharma, Merck Serono, Novartis, Pfizer, Pierre Fabre, Samsung Bioepis 
and Sanofi.

Authorship: All authors have contributed significantly to this publication.

Corresponding Author: Fabienne Zumaglini, Pierre Fabre Dermatologie, Les Cauquillous, 81500 Lavaur, France. Phone: +33 642 44 41 15 
E-mail: fabienne.zumaglini@pierre-fabre.com

Introduction

Dermatological adverse events are commonly experienced 

by patients during anticancer treatment [1, 2].  Xerosis 

is frequently associated with epidermal growth factor 

receptor inhibitor (EGFRi) or mitogen-activated protein 

 kinase  inhibitor (MEKi) treatment [3]. While xerosis is typi-

cally mild-to-moderate in intensity, it can significantly impact 

quality of life [4], especially in patients receiving long-term 

anticancer therapy.



2 Research Letter | Dermatol Pract Concept. 2024;14(4):e2024259

Case Presentation

We conducted a non-interventional prospective pilot study 

at three oncology centers in Italy to identify the proportion 

of patients with emerging or worsening xerosis among those 

receiving targeted anticancer therapies associated with the 

highest risk of xerosis: EGFRis and MEKis. Eligible patients 

were ≥18 years old with cancer initiating treatment with an 

EGFRi or MEKi. Patients were assessed at three study visits 

(Visit 1 was considered baseline). Study assessments included 

xerosis severity (using Overall Dry Skin [ODS] scores and 

Common Terminology Criteria for Adverse Events [CTCAE] 

classifications), skin dryness (using Hydration Index [HI] 

scores), and treatments.

Between 2019 and 2022, 22 patients (mean age 57.3 

years) completed all three study visits. The majority (90.9%) 

received a MEKi (trametinib: n=18, binimetinib: n=2) and 

two (9.1%) patients received an EGFRi (osimertinib). 

 MEKis were administered with a BRAF inhibitor in all 

but one patient. Of these 22 patients, five (22.7%) either 

developed xerosis (n=3; 13.6%, 95% CI: 2.9–34.9) or had 

a worsening of their preexisting xerosis (n=2; 9.1%, 95% 

CI: 1.1–29.2) during treatment (Figure 1). Xerosis severity 

Figure 1. Number of patients who attended all three study visits with 

emerging or worsening xerosis while receiving epidermal growth factor 

receptor or mitogen-activated protein kinase inhibitors (n=22).

Table 1. Outcomes in the Patients Who Attended All 3 Study Visits (n=22).

Visit 1 (BL) Visit 2 Visit 3

Xerosis, n (%) 6 (27.3) 5a (22.7) 8b (36.4)

Xerosis location, n (%)

 Lower limbs 4 (18.2) 4 (18.2) 7 (31.8)

 Upper limbs 3 (13.6) 4 (18.2) 6 (27.3)

 Hands 2 (9.1) 2 (9.1) 3 (13.6)

Emollients, n (%) 7 (31.8) 7 (31.8) 8 (36.4)

 Emollients and topical barrier products 5 (22.7) 6 (27.3) 8 (36.4)

ODS score, mean ± SD 0.32 ± 0.6 0.32 ± 0.6 0.64 ± 1.0

ODS score, n (%)

 0 16 (72.7) 17 (77.3) 14 (63.6)

 1 5 (22.7) 3 (13.6) 3 (13.6)

 2 1 (4.5) 2 (9.1) 4 (18.2)

 3 0 0 1 (4.5)

Xerosis severity, CTCAE classification, n (%)

 Grade 1 6 (27.3) 4 (18.2) 5 (22.7)

 Grade 2 0 1 (4.5) 3 (13.6)

HI score, mean ± SD 38.59 ± 13.36 33.48 ± 11.17 31.66 ± 14.10c

HI score, n (%)

 <30 (very dry) 6 (27.3) 8 (36.4) 10 (47.6)c

 30–45 (dry) 8 (36.4) 11 (50.0) 6 (28.6)c

 >45 (sufficiently hydrated) 8 (36.4) 3 (13.6) 5 (23.8)c

aXerosis resolved in one patient between baseline and Visit 2, then reappeared at Visit 3; bXerosis resolved in one patient after the baseline 
visit; cn=21. Abbreviations: BL: baseline; CTCAE: Common Terminology Criteria for Adverse Events; HI: Hydration Index; ODS: overall 
dry skin; SD: standard deviation.

(CTCAE criteria) was considered Grade 1 in 5 (22.7%) pa-

tients and Grade 2 in 3 (13.6%) patients at Visit 3 (Table 1).  

Approximately one-third of patients received emollient 

treatments during the study (Table 1). HI scores decreased, 

with a mean ± SD change from baseline of –5.10 ± 17.22 and 

–6.30 ± 20.68 at Visits 2 and 3 (Table 1).



Research Letter | Dermatol Pract Concept. 2024;14(4):e2024259 3

Conclusions

Although small and without a control group, this pilot study 

showed that less than one-quarter of patients (22.7%) ini-

tiating EGFRis or MEKis developed xerosis (n=3; 13.6%) 

or experienced worsening of their pre-existing xerosis (n=2; 

9.1%). The incidence of xerosis in the current study was 

broadly similar than that previously reported with other 

targeted anticancer therapies (20.1%–46.5%) [3]. Future re-

search on the frequency and impact of xerosis is warranted in 

a larger cohort of patients receiving EGFRis or MEKis over 

a prolonged treatment period in real-world clinical practice.

The pathogenesis of xerosis is related mostly to the mecha-

nism of action of EGFRis and MEKis, since inhibition of EGFR 

signaling pathway disrupts epidermal differentiation and ho-

meostasis, causing inflammation, ultraviolet sensitivity, dry 

skin, and alterations to skin barrier function [5,6]. Currently, 

there are no guidelines on how to manage xerosis in patients 

receiving anticancer treatments, but an algorithm based on 

CTCAE grading is recommended for early identification and 

prevention of xerosis and others skin complications [3]. Use of 

moisturizers and barrier replacement creams is essential.

While the patients in the current study had xerosis of 

Grade 1 or 2 severity, its associated burden should not be 

underestimated. Prevention, early detection, and treatment 

of xerosis should be appropriately considered.

Acknowledgments: We would like to thank Simone Tait 

of Springer Healthcare Communications, who wrote the 

 outline and subsequent drafts of the letter. Medical writing 

assistance was funded by Pierre Fabre.

References

1. Lacouture M, Sibaud V. Toxic side effects of targeted ther-

apies and immunotherapies affecting the skin, oral mucosa, 

hair, and nails. Am J Clin Dermatol. 2018;19(Suppl 1):31–9.  

DOI: 10.1007/s40257-018-0384-3.

2. Robert C, Soria JC, Spatz A, et al. Cutaneous side-effects of 

 kinase inhibitors and blocking antibodies. Lancet Oncol. 2005; 

6(7):491-500. DOI: 10.1016/S1470-2045(05)70243-6.

3. Valentine J, Belum VR, Duran J, et al. Incidence and risk of 

 xerosis with targeted anticancer therapies. J Am Acad Dermatol. 

2015;72(4):656-667. DOI: 10.1016/j.jaad.2014.12.010.

4. Lee J, Lim J, Park JS, et al. The Impact of Skin Problems on 

the Quality of Life in Patients Treated with Anticancer Agents:  

A Cross-Sectional Study. Cancer Res Treat. 2018;50(4): 

1186-1193. DOI: 10.4143/crt.2017.435.

5. Lacouture ME. Mechanisms of cutaneous toxicities to EGFR in-

hibitors.  Nat Rev Cancer. 2006;6(10):803-812. DOI: 10.1038 

/nrc1970.

6. Pastore S, Lulli D, Girolomoni G. Epidermal growth factor 

receptor signalling in keratinocyte biology: implications for 

skin toxicity of tyrosine kinase inhibitors. Arch Toxicol. 2014; 

88(6):1189-1203. DOI: 10.1007/s00204-014-1244-4.