Salivary duct carcinoma

Salivary duct carcinoma is a high-grade adenocarcinoma of the salivary ducts, usually of the parotid gland in men over sixty, that under the microscope looks like high-grade ductal carcinoma of the breast with comedo necrosis, and sometimes arises within a long-standing pleomorphic adenoma. It spreads early to the neck nodes and to lung and bone, and facial nerve palsy at presentation is common. The great majority of tumours express the androgen receptor, about a third have HER2 amplification, and TP53, PIK3CA and HRAS mutations are frequent, so molecular profiling at diagnosis is standard.

Local treatment is parotidectomy with sacrifice of the facial nerve when it is involved, neck dissection and postoperative radiotherapy or chemoradiation, but most patients relapse at a distance, and systemic treatment borrowed from breast and prostate cancer is what has changed the disease. For HER2-positive tumours a Japanese phase 2 of trastuzumab with docetaxel in 57 patients produced responses in 70.2 percent with median progression-free survival of 8.9 months and median overall survival of 39.7 months, and trastuzumab deruxtecan and trastuzumab emtansine have produced responses in HER2-positive salivary cancers in tumour-agnostic studies.

For androgen receptor-positive disease, a phase 2 of leuprorelin with bicalutamide in 36 patients produced responses in 41.7 percent with median progression-free survival of 8.8 months, and the EORTC 1206 trial randomised androgen deprivation against chemotherapy; enzalutamide gave more modest responses in a phase 2, and apalutamide with a GnRH agonist is in trial. Patients whose tumours have both markers may be treated sequentially, and combined anti-HER2 and anti-androgen treatment is being explored; platinum-based chemotherapy and pembrolizumab for the rare PD-L1-high or mutation-rich tumour are the remaining options.