Top

Published in:

Open Access 01-05-2021 | NSCLC | Original Article

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)

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

Published in: Supportive Care in Cancer | Issue 5/2021

Abstract

Purpose

This 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.

Methods

Patients 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.

Results

Fifty-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.

Conclusion

In NSCLC patients who received EGFRIs, preemptive therapy of oral minocycline and heparinoid moisturizer reduced facial acneiform rash incidence.

Trial registration

UMIN000024113

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957CrossRef

Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31:3327–3334CrossRef

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L, Spanish Lung Cancer Group in collaboration with Groupe Francais de P-C, Associazione Italiana Oncologia T (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13:239–246CrossRef

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T, North-East Japan Study G (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388CrossRef

Peeters M, Oliner KS, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, Andre T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, He P, Yu H, Koukakis R, Terwey JH, Jung AS, Sidhu R, Patterson SD (2015) Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res 21:5469–5479CrossRef

Sorich MJ, Wiese MD, Rowland A, Kichenadasse G, McKinnon RA, Karapetis CS (2015) Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol 26:13–21CrossRef

Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11:21–28CrossRef

Lacouture ME (2006) Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 6:803–812CrossRef

Perez-Soler R, Saltz L (2005) Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol 23:5235–5246CrossRef

10.

Segaert S, Van Cutsem E (2005) Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol 16:1425–1433CrossRef

11.

Kozuki T (2016) Skin problems and EGFR-tyrosine kinase inhibitor. Jpn J Clin Oncol 46:291–298CrossRef

12.

Lacouture ME, Maitland ML, Segaert S, Setser A, Baran R, Fox LP, Epstein JB, Barasch A, Einhorn L, Wagner L, West DP, Rapoport BL, Kris MG, Basch E, Eaby B, Kurtin S, Olsen EA, Chen A, Dancey JE, Trotti A (2010) A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer 18:509–522CrossRef

13.

Joshi SS, Ortiz S, Witherspoon JN, Rademaker A, West DP, Anderson R, Rosenbaum SE, Lacouture ME (2010) Effects of epidermal growth factor receptor inhibitor-induced dermatologic toxicities on quality of life. Cancer 116:3916–3923CrossRef

14.

Rosen AC, Case EC, Dusza SW, Balagula Y, Gordon J, West DP, Lacouture ME (2013) Impact of dermatologic adverse events on quality of life in 283 cancer patients: a questionnaire study in a dermatology referral clinic. Am J Clin Dermatol 14:327–333CrossRef

15.

Tischer B, Huber R, Kraemer M, Lacouture ME (2017) Dermatologic events from EGFR inhibitors: the issue of the missing patient voice. Support Care Cancer 25:651–660CrossRef

16.

Tischer B, Bilang M, Kraemer M, Ronga P, Lacouture ME (2018) A survey of patient and physician acceptance of skin toxicities from anti-epidermal growth factor receptor therapies. Support Care Cancer 26:1169–1179CrossRef

17.

Lacouture ME, Mitchell EP, Piperdi B, Pillai MV, Shearer H, Iannotti N, Xu F, Yassine M (2010) 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 28:1351–1357CrossRef

18.

Hajar T, Leshem YA, Hanifin JM, Nedorost ST, Lio PA, Paller AS, Block J, Simpson EL (2015) A systematic review of topical corticosteroid withdrawal (“steroid addiction”) in patients with atopic dermatitis and other dermatoses. J Am Acad Dermatol 72:541–549 e542CrossRef

19.

Scope A, Lieb JA, Dusza SW, Phelan DL, Myskowski PL, Saltz L, Halpern AC (2009) A prospective randomized trial of topical pimecrolimus for cetuximab-associated acnelike eruption. J Am Acad Dermatol 61:614–620CrossRef

20.

Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS, Investigators F (2017) Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer N Engl J Med

21.

Chu CY, Choi J, Eaby-Sandy B, Langer CJ, Lacouture ME (2018) Osimertinib: a novel dermatologic adverse event profile in patients with lung cancer. Oncologist 23:891–899CrossRef

22.

Takeda M, Okamoto I, Nakagawa K (2015) Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Lung Cancer 88:74–79CrossRef

23.

Nakagawa K, Kudoh S, Ohe Y, Johkoh T, Ando M, Yamazaki N, Seki A, Takemoto S, Fukuoka M (2012) Postmarketing surveillance study of erlotinib in Japanese patients with non-small-cell lung cancer (NSCLC): an interim analysis of 3488 patients (POLARSTAR). J Thorac Oncol 7:1296–1303CrossRef

24.

Kobayashi Y, Komatsu Y, Yuki S, Fukushima H, Sasaki T, Iwanaga I, Uebayashi M, Okuda H, Kusumi T, Miyagishima T, Sogabe S, Tateyama M, Hatanaka K, Tsuji Y, Nakamura M, Konno J, Yamamoto F, Onodera M, Iwai K, Sakata Y, Abe R, Oba K, Sakamoto N (2015) Randomized controlled trial on the skin toxicity of panitumumab in Japanese patients with metastatic colorectal cancer: HGCSG1001 study. J-STEPP Future Oncol 11:617–627CrossRef

25.

Kiyohara Y, Yamazaki N, Kishi A (2013) Erlotinib-related skin toxicities: treatment strategies in patients with metastatic non-small cell lung cancer. J Am Acad Dermatol 69:463–472CrossRef

26.

Melosky B, Anderson H, Burkes RL, Chu Q, Hao D, Ho V, Ho C, Lam W, Lee CW, Leighl NB, Murray N, Sun S, Winston R, Laskin JJ (2016) Pan Canadian Rash Trial: a randomized phase III trial evaluating the impact of a prophylactic skin treatment regimen on epidermal growth factor receptor-tyrosine kinase inhibitor-induced skin toxicities in patients with metastatic lung cancer. J Clin Oncol 34:810–815CrossRef

Title: 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)
Authors: Kazumi Nishino
Yutaka Fujiwara
Yuichiro Ohe
Ryota Saito
Eisaku Miyauchi
Tetsu Kobayashi
Yasuo Nakai
Toshiaki Takahashi
Taro Shibata
Tetsuya Hamaguchi
Katsuko Kikuchi
Naoya Yamazaki
Haruhiko Fukuda
Keiko Nozawa
Yoshio Kiyohara
Publication date: 01-05-2021
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
Minocycline
NSCLC
Heparinoide
Afatinib
Erlotinib
Published in: Supportive Care in Cancer / Issue 5/2021
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-020-05765-7

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Trial registration

Please log in to get access to this content

Other articles of this Issue 5/2021

Prospective patient-reported symptom profiles associated with pediatric acute lymphoblastic leukemia relapse

Navigating cancer treatment and care when living with comorbid dementia: an ethnographic study

Priorities to improve cancer caregiving: report of a caregiver stakeholder workshop

Development and evaluation of a sustainable video health education program for newly diagnosed breast cancer patients in Malaysia

Efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (B-NHL): results of the randomized, open-label, non-inferiority AVOID neutropenia study

Health-related quality of life measured using EQ-5D in patients with lymphomas

Keynote webinar | Spotlight on antibody–drug conjugates in cancer