Lower risk of cutaneous squamous cell carcinomas induced by vemurafenib in non melanoma patients

Abstract

Background: Cutaneous squamous cell carcinomas (cSCCs) occur in about 20% of melanoma (M) patients ( pts) treated with vemurafenib (V), mostly within the first 3 months. We aimed to determine the frequency of cSCCs in non-M pts treated by V in the AcSé-V French national phase II trial and to study their clinical, pathological and molecular characteristics. Methods: Pts included in the AcSé-V trial had a dermatological monitoring under the supervision of the French “Groupe de Cancérologie Cutanée”. Only pts with a follow-up of ≥4 months and without a history of M are included. Pathological reports of resected cSCCs and precursors were analysed by a pathologist. Central pathological review and molecular characterization of cSCCs will be performed. Frequency of cSCCs was compared to BRIM 3 published data. Results: Among 56 pts included in the AcSé trial, six pts (11%; 4F,2M) treated for a BRAF V600E-mutated lung, thyroid or brain tumour developed 10 cutaneous neoplasms. Median size was 5.5 mm (range, 5-10 mm). Location was upper (n = 4) or lower (n = 3) extremities, head and neck (n = 2), and trunk (n = 1). There were 8 cSCCs, 1 papilloma with a keratoacanthoma-like architecture and 1 preepitheliomatous keratosis. Five pts (9%) of median age 76 years old (range, 23-83 years) had cSCCs (multiple cSCCs in 2 pts). Pathological review of cSCCs (7/8 available) showed crateriform (n = 4) or papilliform (n = 2), poorly (n = 1) or well-differentiated (n = 6) cSCCs. The median time to first diagnosis of cSCC or precursor lesion was 71 days (range, 29-161 days); 5/6 pts had a phototype 3; none had a medical history of skin cancer but 3 presented actinic keratosis before V initiation. Conclusions: V-induced cSCCs seem to have similar pathological characteristics in M and non-M pts. The lower frequency of cSCCs in non-M pts compared with M pts in BRIM 3 (p = 0.039) might be due to differences in risk factor frequencies. Potential risk factors of V-induced cSCCs are older age and preexisting actinic keratosis. Analysis of final data might help for dermatological monitoring.