Adenoid cystic carcinoma (ACC) is known to have a poor response to cytotoxic chemotherapy. Multitargeted Tyrosine Kinase inhibitors such as Lenvatinib and Rivoceranib could provide disease control and limited radiographic response in unselected ACC patients. Next-generation sequencing in tissue (tNGS) reveals several MYB gene fusions in ACC, but currently, only NOTCH mutations are being targeted by those agents with limited activity.
We retrospectively reviewed adult patients with a diagnosis of recurrent ACC at the University of Miami Sylvester Comprehensive Cancer Center between January 1, 2019 and October 31, 2020. Commercially available cell free DNA panel of 73 genes was used for analyzing circulating tumor DNA (ctDNA). Patients included had radiographically measurable disease and both tNGS and circulating tumor DNA (ctDNA) data available.
Eleven patients were included. Median age at diagnosis was 56 years (28 - 68), and 64% were males. 82% of the patients had genomic abnormalities reported by tNGS, with the same number by ctDNA sequencing. Five patients (45%) had genomic abnormalities in ctDNA of clinical significance which were not found on tNGS. These genetic abnormalities included mutations in BRAF N581S, FGFR1, FGFR2, JAK2 V617F and MET 273fs genes. Three patients with FGFR genomic abnormalities only seen by ctDNA had been previously treated with Lenvatinib. One patient with primary lacrimal gland ACC metastatic to the liver and tNGS positive for NOTCH 1 had disease progression despite treatment with Lenvatinib and a NOTCH γ-secretase inhibitor. The patient’s ctDNA reported a FGFR2 mutation. He was subsequently started on Erdafitinib, an oral selective FGFR inhibitor currently approved for FGFR positive bladder cancer. The patient achieved a partial response at the primary site and metastatic liver lesions and remained on therapy for 7 months. Follow-up ctDNA after 3 months of therapy noted resolution of both FGFR and NOTCH abnormalities.
Acquired resistance mutations and other genomic abnormalities can develop in patients with ACC after treatment with Multitargeted Tyrosine Kinase inhibitors such as Lenvatinib. ctDNA is now widely available and should be included in the evaluation of patients with recurrent and metastatic ACC. FGFR genomic abnormalities can be a driver mutation in patients with refractory advanced ACC and the activity of Erdafinib should be evaluated in this subset of patients with few therapeutic options.