Vismodegib in neoadjuvant treatment of locally advanced basal cell carcinoma: First results of a multicenter, open-label, phase 2 trial (VISMONEO study)

Autor: Véronique Dziwniel, Alain Duhamel, Nicolas Bertrand, Alain Dupuy, Nicole Basset-Seguin, Laurent Mortier, Philippe Saiag, César Depoortere, S. Dalac-Rat, Pierre Guerreschi
Přispěvatelé: Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS], Hopital Saint-Louis [AP-HP] [AP-HP], Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Universitaire [Rennes], Service de Dermatologie (CHU de Dijon), Centrale Lille, Service de Biostatistiques [CHRU Lille], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 (MBLC - ADDS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Université de Lille, Inserm, CHU Lille
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: EClinicalMedicine
EClinicalMedicine, 2021, 35, pp.100844. ⟨10.1016/j.eclinm.2021.100844⟩
EClinicalMedicine, Vol 35, Iss, Pp 100844-(2021)
ISSN: 2589-5370
DOI: 10.1016/j.eclinm.2021.100844⟩
Popis: Background Surgery is the primary treatment for basal cell carcinoma (BCC). In locally advanced basal cell carcinoma (laBCC), surgery may cause functional or aesthetic damage. In laBCC, neoadjuvant administration of vismodegib, an inhibitor of the Hedgehog signaling pathway, may reduce tumor size, facilitate resection, and reduce functional and aesthetic consequences of surgery. The VISMONEO study assessed efficacy and safety of vismodegib in neoadjuvant treatment of laBCC. Methods VISMONEO (NCT02667574) is an open-label, noncomparative, multicenter, phase 2 study. Patients with ≥1 histologically confirmed facial BCC, inoperable or operable with functional or major aesthetic sequelae risk, were included. Oral vismodegib 150 mg was administered once daily for 4 to 10 months before planned surgery, which was performed once the best response under vismodegib was observed. Primary endpoint was percentage of patients with BCC with tumor downstaging following surgical resection after neoadjuvant vismodegib. Downstaging was defined according to a 6-stage surgical classification related to the aesthetic and functional consequences of surgery. Findings 55 patients (median age: 73 years) with laBCC were included from November 2014 to June 2015. At inclusion, 4 patients were inoperable, 15 were operable with a major functional risk, and 36 were operable with a minor functional risk or a major aesthetic risk. Mean size of target lesion was 47.3 mm (SD: 27.2 mm). 44 patients presented with downstaging after vismodegib treatment (80%; 95% confidence interval [CI], 67 to 90). Of these 44 patients, 27 had a complete response (25 proved by biopsy). Mean treatment duration was 6.0 months. Overall Response Rate according to RECIST 1.1 criteria was 71% (95% CI, 59 to 88). At 3-years of follow-up, 16/44 patients had known recurrence (36%; 95%CI, 22 to 51). Interpretation Neoadjuvant vismodegib allows for a downstaging of the surgical procedure for laBCCs in functionally sensitive locations. Funding VISMONEO was funded by F. Hoffmann-La Roche Ltd.
Databáze: OpenAIRE
Externí odkaz: