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Genomic landscape of advanced basal cell carcinoma: Implications for precision treatment with targeted and immune therapies.


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.

SUBMITTER: Goodman AM 

PROVIDER: S-EPMC5790366 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Genomic landscape of advanced basal cell carcinoma: Implications for precision treatment with targeted and immune therapies.

Goodman Aaron M AM   Kato Shumei S   Cohen Philip R PR   Boichard Amélie A   Frampton Garrett G   Miller Vincent V   Stephens Philip J PJ   Daniels Gregory A GA   Kurzrock Razelle R  

Oncoimmunology 20171222 3


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 tumor  ...[more]

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