PMID- 34689002 OWN - NLM STAT- MEDLINE DCOM- 20220324 LR - 20220324 IS - 2059-7029 (Electronic) IS - 2059-7029 (Linking) VI - 6 IP - 6 DP - 2021 Dec TI - Efficacy of sonic hedgehog inhibitors rechallenge, after initial complete response in recurrent advanced basal cell carcinoma: a retrospective study from the CARADERM database. PG - 100284 LID - S2059-7029(21)00246-5 [pii] LID - 10.1016/j.esmoop.2021.100284 [doi] LID - 100284 AB - 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. CI - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Bassompierre, A AU - Bassompierre A AD - Department of Dermatology, Lille University, CHU Lille, Lille, France. Electronic address: a.bassompierre@gmail.com. FAU - Dalac, S AU - Dalac S AD - Department of Dermatology, Dijon University Hospital, Dijon, France. FAU - Dreno, B AU - Dreno B AD - Department of Dermatology, Dieu Hospital, Nantes, France. FAU - Neidhardt, E M AU - Neidhardt EM AD - Department of Dermatology, Leon Berard Center, Lyon, France. FAU - Maubec, E AU - Maubec E AD - Department of Dermatology, AP-HP, Avicenne University Hospital, Bobigny, France. FAU - Capelle, C AU - Capelle C AD - Department of Dermatology, Lille University, CHU Lille, Lille, France. FAU - Andre, F AU - Andre F AD - Department of Dermatology, Lille University, CHU Lille, Lille, France. FAU - Behal, H AU - Behal H AD - Health Technology and Medical Practice Assessment, ULR 2694-METRICS, Lille University Hospital, University of Lille, Lille, France. FAU - Dziwniel, V AU - Dziwniel V AD - Department of Dermatology, Lille University, CHU Lille, Lille, France; Languages Department, Centrale Lille Institut, Villeneuve d'Ascq, France. FAU - Bens, G AU - Bens G AD - Department of Dermatology, Orleans Regional Hospital, Orleans, France. FAU - Leccia, M T AU - Leccia MT AD - Department of Dermatology, Grenoble University Hospital, Grenoble, France. FAU - Meyer, N AU - Meyer N AD - Department of Dermatology, IUC and CHU de Toulouse, Toulouse, France. FAU - Granel-Brocard, F AU - Granel-Brocard F AD - Department of Dermatology, Nancy University Hospital, Nancy, France. FAU - Beylot-Barry, M AU - Beylot-Barry M AD - Department of Dermatology, Bordeaux University Hospital, Bordeaux, France. FAU - Dereure, O AU - Dereure O AD - Department of Dermatology, University of Montpellier, Montpellier, France. FAU - Basset-Seguin, N AU - Basset-Seguin N AD - Department of Dermatology, Saint-Louis Hospital, AP-HP, Paris University Hospital, Paris, France. FAU - Mortier, L AU - Mortier L AD - Department of Dermatology, Lille University, CHU Lille, Lille, France; INSERM U1189, CARADERM, CHU Lille, Lille, France. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20211021 PL - England TA - ESMO Open JT - ESMO open JID - 101690685 RN - 0 (Antineoplastic Agents) RN - 0 (Hedgehog Proteins) SB - IM MH - *Antineoplastic Agents/adverse effects MH - *Carcinoma, Basal Cell/drug therapy/pathology MH - Hedgehog Proteins/physiology/therapeutic use MH - Humans MH - Neoplasm Recurrence, Local/chemically induced/drug therapy MH - Retrospective Studies MH - *Skin Neoplasms/drug therapy PMC - PMC8551849 OTO - NOTNLM OT - CARADERM OT - SMO inhibitor OT - advanced BCC OT - rechallenge OT - recurrence OT - relapse OT - resistance OT - retreatment OT - vismodegib COIS- Disclosure EMN: Consulting or advisory role: Novartis, Pierre Fabre, Bristol-Myers Squibb, MSD. EM: Consulting or advisory role: MSD, Pierre Fabre, Novartis, Sanofi; research funding: MSD (Inst); travel, accommodations, expenses: MSD Oncology, Pierre Fabre, Novartis. NM: Consulting or advisory role or research funding: Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Merck, Sanofi, Sun Pharmaceutical Industries. MB-B: Research funding: Roche; consulting or advisory role: Sun Pharmaceutical Industries. NB-S: Consulting or advisory role: Sanofi, Sun Pharmaceutical Industries. LM: Consulting or advisory role: Sanofi, Sun Pharmaceutical Industries, MSD Oncology, Bristol-Myers Squibb, Novartis. The remaining authors have declared no conflicts of interest. EDAT- 2021/10/25 06:00 MHDA- 2022/03/25 06:00 PMCR- 2021/10/21 CRDT- 2021/10/24 20:42 PHST- 2021/07/06 00:00 [received] PHST- 2021/09/12 00:00 [revised] PHST- 2021/09/22 00:00 [accepted] PHST- 2021/10/25 06:00 [pubmed] PHST- 2022/03/25 06:00 [medline] PHST- 2021/10/24 20:42 [entrez] PHST- 2021/10/21 00:00 [pmc-release] AID - S2059-7029(21)00246-5 [pii] AID - 100284 [pii] AID - 10.1016/j.esmoop.2021.100284 [doi] PST - ppublish SO - ESMO Open. 2021 Dec;6(6):100284. doi: 10.1016/j.esmoop.2021.100284. Epub 2021 Oct 21.