Clinical utility of comprehensive genomic profiling for skin cancer: A cohort study of 522 cases in a Japanese real-world setting

• Published in: EJC skin cancer 2024-12, Vol.2, p.100259, Article 100259
• Main Authors: Iwasawa, Okuto, Miyagawa, Takuya, Awaji, Kentaro, Omatsu, Jun, Yamada, Daisuke, Sumida, Hayakazu, Kage, Hidenori, Oda, Katsutoshi, Sato, Shinichi
• Format: Article
• Language: English
• Subjects: Molecular targeted therapy; Precision medicine; Skin neoplasms
• ISSN: 2772-6118; 2772-6118
• DOI: 10.1016/j.ejcskn.2024.100259

Advanced cases of skin cancer sometimes represent a clinical challenge to treat due to limited approved treatments. Comprehensive genomic profiling (CGP) tests are indicated for metastatic or unresectable cases; however, their results and clinical utility in skin cancer remain unclear. This is a retrospective cohort study analyzing the CGP test results of 522 cases of skin cancer submitted between June 2019 and November 2022 using a nationwide database recording clinical data and CGP test results in Japan. 522 cases were registered. In cancer types, the most prevalent was cutaneous melanoma (CM, n=235), followed by cutaneous squamous cell carcinoma (cSCC, n=91), Extramammary Paget’s disease (EMPD, n=75), adnexal carcinoma (AC, n=58), cutaneous angiosarcoma (cAS, n=33), basal cell carcinoma (BCC, n=15), Merkel cell carcinoma (n=10) and dermatofibrosarcoma protuberans (n=5). The median TMB was highest in EMPD and cAS (5.0 mutations/Mb), whereas high TMB cases (≥10.0 mutations/Mb) were most prevalent in BCC (33 %), followed by cSCC (26 %). No cases were classified as MSI-high. NTRK1/2/3 fusions were identified in two cases: one CM and one AC. BRAF V600E mutations in non-melanoma skin cancer were observed in one case of AC. Actionable genetic alterations eligible for ongoing clinical trials utilizing unapproved drugs were found most frequently in EMPD (51 %), followed by BRAF V600E/K-negative CM (44 %). This study provides an overview of CGP test results and identifies potential therapeutic targets for each type of skin cancer. These findings improve our understanding of CGP test outcomes and advance tailored therapies for skin cancer.