Genomic landscape of advanced basal cell carcinoma: Implications for precision treatment with targeted and immune therapies. (4th March 2018)

• Record Type: Journal Article
• Authors: Goodman, Aaron M.; Kato, Shumei; Cohen, Philip R.; Boichard, Amélie; Frampton, Garrett; Miller, Vincent; Stephens, Philip J.; Daniels, Gregory A.; Kurzrock, Razelle
• Is Part Of: Oncoimmunology. Volume 7:Number 3(2018)
• Publication Date: 2018-03-04
• Subjects: Basal cell carcinoma -- Immunotherapy -- tumor mutational burden -- PD-1 -- PD-L1 -- Checkpoint blockade -- Biomarkers -- Therapeutic antibodies; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1404217
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Metastatic basal cell cancer (BCC) is an ultra-rare malignancy with no approved therapies beyond Hedgehog inhibitors. We characterized the genomics, tumor mutational burden (TMB), and anti-PD-1 therapy responses in patients with locally advanced or metastatic BCC. Overall, 2, 039 diverse cancer samples that had undergone comprehensive genomic profiling (CGP) were reviewed. Eight patients with locally advanced/metastatic BCC were identified (two had two CGP analyses; total, 10 biopsies). Two tumors demonstrated PD-L1 amplification. Seven patients had >1 actionable alteration. The TMB (mutations/mb) (median (range)) was 90 (3-103) for the BCCs versus 4 (1-860) for 1637 cancers other than BCC (P < 0.0001). Median progression-free survival (PFS) for all four patients treated with PD-1 blockade was 10.7 months (range, 3.8 to 17.6+ months); three patients had an objective response. In conclusion, advanced/metastatic BCC often has biological features (high TMB; PD-L1 amplification) predictive of immunotherapy benefit, and patients frequently respond to PD-1 blockade.