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

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.

Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma.

Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.

Systematic skin examination in an acute geriatric unit: skin cancer prevalence.

BACKGROUND: Ageing is a determining factor in skin cancer, but the incidence and prevalence of skin cancer in elderly patients are not known. AIM: To determine the prevalence of skin cancers in elderly patients and to assess their associated geriatric syndromes. METHODS: Between January and April 2013, all consecutive incident patients hospitalized in the Acute Geriatric Unit of Lille University Hospital underwent a geriatric assessment and a systematic dermatological examination. A biopsy was taken whenever there was any lesion with suspicion of malignancy. RESULTS: In total, 204 patients (mean age 85.4 years) were included, and 16 cutaneous biopsies were taken from 15 patients. Histological examination confirmed skin cancer in 11 biopsies from 10 patients: 9 basal cell carcinomas, 1 squamous cell carcinoma (SCC) and 1 malignant lentigo. The prevalence of skin cancer was 4.9%. The geriatric assessment revealed severe geriatric syndromes in the 10 patients with skin cancer: severe dependence (8/10), possible cognitive impairment (10/10), and moderate or severe malnutrition (5/10). CONCLUSIONS: The prevalence of skin cancer is high in frail elderly patients. The association of severe geriatric syndromes suggests that close collaboration between geriatricians and dermatologists is essential to optimize the treatment of skin carcinoma in elderly patients.