56-year-old man diagnosed in January 2019 with parotid ductal-type adenocarcinoma E-IVA (pT1 pN3b cM0) after complete parotidectomy with left functional dissection. Adjuvant treatment with platinum-based chemoradiotherapy was planned, but patient declined and preferred surveillance. 16 months later, in June 2020, locoregional and lung progression was observed in CT-scan. First line treatment with Carboplatin-Paclitaxel was started, achieving partial response after 6 cycles. In May 2021, after 6-month follow-up, CT-scans show new lung disease progression. 2nd line treatment with 6 cycles of Adriamycin delivered a stable disease. In January 2022 pulmonary progression was confirmed. On no possibility of tumor rebiopsy, primary tumor tissue was deeply reanalyzed: Next Generation Sequencing (NGS) showed PIK3CA and TP53 mutations; and immunohistochemistry (IHC), overexpression of HER2, with negative expression of estrogen (ER) and progesterone (PR) receptors. Trastuzumab + Pertuzumab was started in February 2022. After 3 cycles, with good tolerance to treatment without relevant toxicities, re-evaluation CT confirmed progression of lung disease. Upon request of the patient, who remains asymptomatic, considering a slow progressing disease, a watch and wait strategy has been adopted, and further treatment options (alpelisib, capecitabine…) would be discussed when necessary.
Although chemotherapy has been considered standard of care in salivary gland carcinomas (SGC), different subtypes harbor different molecular alterations, potentially actionable. HER2 overexpression in SGD ranges from 15% to 44%, with recurrence, distant metastases, and poorer survival rates. Recent studies show improvement in tumor control rate and prognosis of SGC HER2+ by adding trastuzumab to treatment as monotherapy or in combination with chemotherapy and/or pertuzumab. Other alterations such as PI3K mutations have been reported in up to 53% of SGC cases, conferring a potentially beneficial and yet poorly explored therapeutic strategy in SGC.