The Role of Immunotherapy in Salivary Gland Cancer: A Systematic Review

Background: Salivary gland cancer (SGC) comprises a very heterogeneous group of rare neoplasms, accounting for approximately 2% to 6% of head and neck malignancies. Surgery with or without adjuvant radiotherapy is the main treatment regimen. However, patients who are ineligible for surgery, including late-stage, recurrent, or metastatic disease, have very limited options. Chemotherapeutic schemes have failed to offer meaningful survival benefit, while the role of immune checkpoint inhibitors (ICIs) like anti-PD1, anti-PDL1, and anti-CTLA4 is largely unknown. Methods: A systematic database search of clinical trials evaluating the role of anti-PD1 and anti-CTLA4 immunotherapy in the survival of patients with SGC was conducted in EMBASE, MEDLINE, and Scopus databases. Primary outcomes were overall survival, progression-free survival, complete responses (CRs), partial responses (PRs), stable disease (SD), and objective response rates. Results: We identified 770 relevant studies. Nine clinical trials and 4 retrospective studies met the inclusion criteria and were eligible for further analysis. A total of 473 patients were studied, with an average age of 61 ± 4 years old for prospective trials and 60 ± 11 years old for retrospective studies. For studies that provided gender, the male-to-female ratio was 1.2:1 for prospective trials versus 4:1 for retrospective studies. All patients in the clinical trials had recurrent or metastatic disease. All patients received anti-PD1 ICI with either pembrolizumab or nivolumab, 7 study arms administering pembrolizumab, 10 study arms administering nivolumab. For prospective trials, 6/9 studies also reported an additional intervention. Most prevalent histology was adenoid cystic carcinoma (n = 230). Outcome of prospective trial were 1 CR, 19 PRs 145 SD, and 80% of patients reporting an adverse event (AE) of any grade. For retrospective studies, 1 patient reported CR, 3 patients reported PR, 11 patients reported SD, and 92% of patients reported an AE of any grade. Conclusion: Anti-PD1 immunotherapeutic modalities can be a safe and potentially-beneficial option for patients with advanced, recurrent, or metastatic SGC. However, the literature suffers from small cohorts, lack of randomization, and heterogeneity among different histologies of SGC. Prospective trials evaluating the role of anti-PD1 in patients with SGC, stratified by histology are warranted to determine the potential role of immunotherapy in the treatment of this disease.