Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

Abstract

The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT), followed by maintenance cetuximab (the “EXTREME” regimen). This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%. Furthermore, as indicated by patient-reported outcome measures, the addition of cetuximab to platinum-based CT leads to a significant reduction in pain and problems with social eating and speech. Conversely, until very recently, there has been a lack of evidence-based second-line treatment options, and the therapies that have been available have shown low response rates and poor survival outcomes. Presently, a promising new treatment option in R/M SCCHN has emerged: immune checkpoint inhibitors (ICIs), which have demonstrated favorable results in second-line clinical trials. Nivolumab and pembrolizumab are the first two ICIs that were approved by the US Food and Drug Administration. We note that the trials that showed benefit with ICIs included not only patients who previously received ≥1 platinum-based regimens for R/M SCCHN but also patients who experienced recurrence within 6 months after combined modality therapy with a platinum agent for locally advanced disease. In this review, we outline the available clinical and observational evidence for the EXTREME regimen and the initial results from clinical trials for ICIs in patients with R/M SCCHN. We propose that these treatment options can be integrated into a new continuum of care paradigm, with first-line EXTREME regimen followed by second-line ICIs. A number of ongoing clinical trials are comparing regimens with ICIs, alone and in combination with other ICIs or CT, with the EXTREME regimen for first-line treatment of R/M SCCHN. As we eagerly await the results of these trials, the EXTREME regimen remains the standard of care for the first-line treatment of R/M SCCHN.

Prognostic role of epiregulin/amphiregulin expression in recurrent/metastatic head and neck cancer treated with cetuximab

“…In the treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), Vermorken et al reported in 2008 that the EXTREME regimen prolonged OS when given as first‐line treatment for R/M HNSCC . Although there is a worldwide effort to prolong survival for such patients, the regimen remains the standard for R/M HNSCC . Predictive biomarkers for the efficacy of cetuximab regimens in head and neck cancer are thus needed to improve both the therapeutic index and cost‐effectiveness, as well as to increase our understanding of resistance pathways to aid future drug development.…”

Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-β-hydroxymaytenin Obtained from Cultivated Maytenus ilicifolia Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p

“…Platinum-based chemoradiation is the standard treatment for patients with locoregionally advanced, recurrent and/or metastatic HNSCC. Possibly, the major development in first-line treatment for these cases in the past decade was the introduction of cetuximab-a monoclonal antibody which binds to the extracellular domain of the human epidermal growth factor receptor-in combination with platinum chemotherapy [16]. Despite the reported improvements in survival and life quality, the cost-effectiveness of the introduction of cetuximab in developing countries, including Brazil, is mostly unknown.…”

Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma

“…The risk factors of distant metastasis for head and neck SCC (HN-SCC) are related to age, the site of the primary cancer, local and/or regional extension, and histologic grading (15). Patients with localized HN-SCC are treated with potentially curative therapy using treatment modalities that include surgery, radiotherapy, chemotherapy, and biologic therapy (16). The recurrence rate in early-stage HN-SCC ranges from 10% to 20%, and the recurrence rate in locally advanced HN-SCC exceeds 50%.…”