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Efficacy of sonic hedgehog inhibitors rechallenge, after initial complete response in recurrent advanced basal cell carcinoma: a retrospective study from the CARADERM database
- Source :
- ESMO Open
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- 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.<br />Highlights • Real-world experience of SMOis in a French national multicenter and retrospective study. • Efficacy and tolerance detailed in rechallenge, with long-term evolution. • Focus on a population with Gorlin syndrome.
- Subjects :
- Cancer Research
recurrence
Skin Neoplasms
rechallenge
Vismodegib
Antineoplastic Agents
computer.software_genre
Sonidegib
resistance
chemistry.chemical_compound
vismodegib
medicine
Humans
advanced BCC
Hedgehog Proteins
Basal cell carcinoma
Sonic hedgehog
Adverse effect
Original Research
Retrospective Studies
relapse
Database
biology
CARADERM
business.industry
Retrospective cohort study
medicine.disease
Hedgehog signaling pathway
Discontinuation
SMO inhibitor
Oncology
chemistry
Carcinoma, Basal Cell
biology.protein
Neoplasm Recurrence, Local
retreatment
business
computer
medicine.drug
Subjects
Details
- ISSN :
- 20597029
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- ESMO Open
- Accession number :
- edsair.doi.dedup.....ebf965458dbc4439ee12421dc3dc35fd