Systemic therapy in the management of recurrent or metastatic salivary duct carcinoma: A systematic review

Abstract

Background: Salivary duct carcinoma (SDC) is an aggressive subtype of salivary gland cancer. Approximately half of SDC patients will develop recurrences or metastases. Therapeutic palliative therapy is therefore often needed. The majority of SDC tumors expresses the androgen receptor (AR) and one-third expresses human epidermal growth factor receptor 2 (HER2), both are potential therapeutic targets. The aim of this paper is to systematically review and summarize the evidence on systemic palliative therapy for SDC and to provide treatment recommendations. Materials and methods: Electronic libraries were systematically searched with a broad search strategy to identify studies where SDC patients received systemic therapy. Due to the rarity of SDC no restrictions were placed on study designs. Results: The search resulted in 2014 articles of which 153 were full-text analyzed. Forty-five studies were included in the analysis, which included in total 256 SDC patients receiving systemic therapy. Two phase 2 trials primarily including SDC patients were identified. The majority of the studies were case series or case reports, resulting in an overall low quality of available evidence. Based on studies including ≥ 5 SDC patients, objective responses to HER2 targeting agents were observed in 60-70%, to AR pathway agents in 18-53% and to chemotherapy in 10-50%. Conclusion: For AR or HER2 positive SDC, agents targeting these pathways are the cornerstone for palliative treatment. Regarding chemotherapy, the combination of carboplatin combined with a taxane is best studied. Regarding other targeted agents and immunotherapy evidence is anecdotal, limiting formulation of treatment recommendations for these antineoplastic agents.

Multicentre, retrospective study of the efficacy and safety of nivolumab for recurrent and metastatic salivary gland carcinoma

“…In contrast, ICIs might be tried in patients with SGC without targetable molecules instead of conventional cytotoxic anticancer agents. Recent studies reported that cytotoxic anticancer agents seemed to achieve a higher ORR with higher toxicity than the ICIs 3,4,24,25 . However, it is difficult to directly compare those therapies as patient background (e.g., histological type) might differ.…”

“…recommended for patients at a high risk of recurrence 3 . Numerous clinical trials of cytotoxic chemotherapies have been conducted in patients with recurrent and/or metastatic (R/M) SGC 3,4 and several potential targets for systemic therapy have been reported [5][6][7][8][9][10][11][12][13][14][15][16][17] ; however, there were no randomised controlled trials 3,4 . Moreover, unlike lung metastasis of adenoid cystic carcinoma (AdCC), majority of which show indolent growth 3,18,19 , the progression of salivary duct carcinoma (SDC) and adenocarcinoma, not otherwise specified (NOS) is aggressive 3,20,21 .…”

Excellent Response With Alpelisib and Bicalutamide for Advanced Salivary Duct Carcinoma With PIK3CA Mutation and High Androgen Receptor Expression—A Case Report

“… 11 A nationwide case series involving 35 patients with AR-positive aSDC treated with either monotherapy (luteinizing hormone-releasing hormone analogues or the AR antagonists: enzalutamide or bicalutamide) or combined androgen blockade (luteinizing hormone-releasing hormone analogue and bicalutamide) had a clinical benefit rate of 50%. 10 , 12 …”

Patients with Rare Head Neck Cancers: Do They Need a Different Approach?

“…This includes mutations in TP53 (53-68%), PIK3CA (18-26%), HRAS (16-23%), BRAF (4%) and AKT1 (1.5%). Reports on the use of drugs aiming at these targets in clinical practice are scarce [12].…”