Efficacy of sonic hedgehog inhibitors rechallenge, after initial complete response in recurrent advanced basal cell carcinoma: a retrospective study from the CARADERM database

ESMO Open

article

A. Bassompierre¹  S. Dalac²  B. Dreno³  E.M. Neidhardt⁴  E. Maubec⁵  C. Capelle¹  F. Andre¹  H. Behal⁶  V. Dziwniel¹  G. Bens⁸  M.T. Leccia⁹  N. Meyer^1,10  F. Granel-Brocard^1,11  M. Beylot-Barry^1,12  O. Dereure^1,13  N. Basset-Seguin^1,14  L. Mortier¹ 

[1] Department of Dermatology, Lille University;Department of Dermatology, Dijon University Hospital;Department of Dermatology, Dieu Hospital;Department of Dermatology, Léon Bérard Center;Department of Dermatology, AP-HP, Avicenne University Hospital;Health Technology and Medical Practice Assessment, ULR 2694-METRICS, Lille University Hospital, University of Lille;Languages Department, Centrale Lille Institut;Department of Dermatology, Orleans Regional Hospital;Department of Dermatology, Grenoble University Hospital;Department of Dermatology;Department of Dermatology, Nancy University Hospital;Department of Dermatology, Bordeaux University Hospital;Department of Dermatology, University of Montpellier;Department of Dermatology, Saint-Louis Hospital, AP-HP, Paris University Hospital;INSERM U1189

关键词: advanced BCC;    SMO inhibitor;    vismodegib;    recurrence;    relapse;    retreatment;    rechallenge;    resistance;    CARADERM;   

DOI  :  10.1016/j.esmoop.2021.100284

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Smoothened (SMO) inhibitors, blocking the sonic hedgehog pathway, have been approved for advanced basal cell carcinoma (aBCC). Safety analyses reveal a high rate of adverse events (AEs) and, most of the time, vismodegib is most commonly stopped when the best overall response is reached. The long-term evolution of aBCC after vismodegib discontinuation is poorly described. The aim of this study is to evaluate the efficacy and safety of the SMO inhibitors (SMOis) available (vismodegib and sonidegib) following rechallenge after complete response (CR) following an initial treatment by vismodegib.Materials and methods This real-life, retrospective, multicenter and descriptive study is based on an extraction from the CARADERM accredited database, including 40 French regional hospitals, of patients requiring BCC systemic treatment.Results Of 303 patients treated with vismodegib, 110 achieved an initial CR. The vast majority of these patients (98.2%) stopped vismodegib, notably due to poorly tolerated AEs. The CARADERM database provided a median follow-up of 21 months (13.5-36.0 months) after CR. Of the 110 patients, 48.1% relapsed after a median relapse-free survival of 24 months (13.0-38.0 months). Among them, 35 patients were retreated by an SMOi and the overall response rate was 65.7% (34.3% of CR and 31.4% of partial response). The median duration of retreatment was 6.0 months (4.0-9.5 months).Conclusion Our real-life study, carried out on patients with complex clinical pictures, shows that after treatment discontinuation, 48.1% of patients achieved CR relapse within an average of 24 months (13.0-38.0 months). It emphasized that even though rechallenge can be considered as a therapeutic option, efficacy seems to decrease, suggesting the development of resistance mechanisms.

【 授权许可】

CC BY|CC BY-NC-ND