Therapeutic Potential of Antibody-Drug Conjugate-Based Therapy in Head and Neck Cancer: A Systematic Review

SIMPLE SUMMARY: Head and neck cancer (HNC) is a complex and extremely heterogeneous disease that includes a wide variety of cancer subtypes. Despite notable advances in understanding the molecular mechanisms involved in the disease, which allowed the increase of the therapeutic armamentarium, HNC treatment remains very challenging. In fact, to date the average 5-year survival rate for this disease is around 65%; hence, HNC continues to be one of the most aggressive solid tumors. Surgical removal is the first treatment of choice for HCN; however, in addition to this treatment modality, a broad spectrum of new therapies has been developed so far, ranging from multimodal chemotherapy to targeted and immune-therapy, mainly through the use of antibodies. In this work, we systematically reviewed the progress obtained in antibody-drug conjugate (ADC) development for the treatment of HNC. ABSTRACT: Background: Antibody-drug conjugates (ADCs) are designed to deliver potent cytotoxic agents into tumor tissues. During the last two decades, a plethora of ADCs have been successfully developed and used for several indications, including hematologic and solid tumors. In this work, we systematically reviewed the progress in ADC development for the treatment of HNC. Methods: This review was registered in PROSPERO database. A comprehensive search was conducted following PRISMA guidelines and using PubMed, Scopus and Web of Science database. Results: In total, 19 studies were included. Due to the significant heterogeneity of the outcome measures, meta-analysis was not performed, and data were summarized in tables. HNC results are poorly represented in the cohorts of completed clinical trials; published data are mostly focused on safety evaluation rather than efficacy of ADCs. Conclusions: Although several novel agents against a wide range of different antigens were investigated, showing promising results at a preclinical level, most of the targets reported in this review are not specific for HNC; hence, the development of ADCs tailored for the HNC phenotype could open up new therapeutic perspectives. Moreover, the results from the present systematic review call attention to how limited is the application of current clinical trials in HNC.