A new clinical case study published in a research letter in JAMA Oncology shows a beneficial clinical outcome for a patient with a rare tumor type as a result of comprehensive genomic profiling with FoundationOne. The patient, a woman in her 30’s, was diagnosed with an advanced acinic cell tumor of the right parotoid gland – a very rare type of cancer. Her disease progressed despite initial treatments with chemotherapy, followed by erlotinib. At the time of disease progression, FoundationOne identified a BRAF kinase domain-duplication (BRAF-KD) as the sole oncogenic driver of her cancer, which suggested regorafinib as a viable treatment option. As a result of treatment, the patient achieved a significant partial response in all disease sites, and continues to maintain a partial response lasting more than a year with regorafenib therapy.
BRAF is the most potent activator of MEK kinases, and alterations in the Ras-Raf-MEK-ERK pathway are observed in nearly 30% of cancers. More than 300 BRAF mutations have been described across all cancers; however, BRAF-KD was previously only observed in gliomas. To identify additional BRAF-KD events, Foundation Medicine interrogated data from 50,000 clinical samples profiled by FoundationOne in the company’s knowledgebase, FoundationCORE. BRAF-KD represented 0.5% of BRAF alterations and had not been identified in the available Catalogue of Somatic Mutations in Cancer or The Cancer Genome Atlas (TCGA) data.
Notably, this is the first report and largest series examining BRAF-KDs, providing evidence that BRAF-KDs are a clinically important genomic alteration and therapeutic target across multiple tumor types. Increasing clinical adoption of FoundationOne is likely to further define BRAF-KDs, a promising step forward for patients harboring these genomic alterations.