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

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.

Clinical trial identification

NCT02304809

Legal entity responsible for the study

UNICANCER, GCC

Funding

UNICANCER

Disclosure

X. Troussard: Advisory Board : Gilead. Roche. Janssen. S. Leboulleux: Consulting : Genzyme, Sanofi, Astra Zeneca. Travel : Genzyme, Sanofi, Bayer. D. Malka: Honoraria : Roche, Amgen, Bayer, Teva, Celgene, Lilly, Merck, Merck Serono, Sanofi-Aventis. Consulting : Roche, Merck. Travel : Roche, Sanofi-Aventis. S. Dalle: Received research grant from Roche-Genentech. J-Y. Blay: Advisory Board: Roche, Novartis, Bayer, MSD, Lilly, Pharmamar, Deciphera. Corporate-sponsored Research: Roche, Novartis, Bayer, MSD, Lilly, Pharmamar. All other authors have declared no conflicts of interest.