The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Abstract

Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab - for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens. The European Commission followed in 2017 with approval of nivolumab for treatment of the same patient population, and shortly thereafter with approval of pembrolizumab monotherapy for the treatment of recurrent or metastatic HNSCC in adults whose tumors express PD-L1 with a ≥ 50% tumor proportion score and have progressed on or after platinum-containing chemotherapy. Then in 2019, the FDA granted approval for PD-1 inhibition as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC, approving pembrolizumab in combination with platinum and fluorouracil for all patients with HNSCC and pembrolizumab as a single agent for patients with HNSCC whose tumors express a PD-L1 combined positive score ≥ 1. These approvals marked the first new therapies for these patients since 2006, as well as the first immunotherapeutic approvals in this disease. In light of the introduction of these novel therapies for the treatment of patients with head and neck cancer, The Society for Immunotherapy of Cancer (SITC) formed an expert committee tasked with generating consensus recommendations for emerging immunotherapies, including appropriate patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing. These consensus guidelines serve as a foundation to assist clinicians' understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit. Due to country-specific variances in approvals, availability and regulations regarding the discussed agents, this panel focused solely on FDA-approved drugs for the treatment of patients in the U.S.

Keywords: Guidelines; Head and neck cancer; Head and neck squamous cell carcinoma (HNSCC); Immune checkpoint inhibitor (ICI); Immunotherapy.

Fig. 1

Treatment Algorithm 1: First-line treatment for R/M HNSCC patients. Immunotherapy treatment algorithm for R/M Systemic Therapy Naïve HNSCC. This treatment strategy takes into account recent data from the Keynote-048 trial and would be reasonable if pembrolizumab is available. All treatment options shown may be appropriate. The final selection of therapy should be individualized based on patient eligibility and therapy availability based on the treating physician’s discretion. The goal of these algorithms are to provide advice as the consensus recommendations of the Subcommittee. 1) Treating physician will determine if patient is fit to undergo pembrolizumab monotherapy or pembrolizumab/cisplatin/5-FU combination therapy as first-line therapy for R/M HNSCC. 2) If patient experiences disease progression on or after pembrolizumab monotherapy, patient should receive platinum based chemotherapy or be enrolled in an appropriate clinical trial. 3) If patient experiences disease progression on or after pembrolizumab/cisplatin/5-FU combination therapy, patient may receive second-line non-platinum based chemotherapy/cetuximab or be enrolled in an appropriate clinical trial. In addition, patients are eligible for nivolumab or pembrolizumab regardless of PD-L1 expression, according to the 2016 FDA approvals of nivolumab and pembrolizumab for second-line treatment of patients with HNSCC. *Clinical trials, including those that are immunotherapy-based, should be considered in all HNSCC patients, in all lines of therapy

Fig. 2

Treatment Algorithm 2: Second-line treatment for R/M HNSCC patients. Immunotherapy treatment algorithm for platinum-refractory recurrent/metastatic HNSCC based on current FDA approvals for pembrolizumab and nivolumab as second-line therapies. All treatment options shown may be appropriate. The final selection of therapy should be individualized based on patient eligibility and therapy availability based on the treating physician’s discretion. The goal of these algorithms are to provide advice as the consensus recommendations of the Subcommittee. 1) Nivolumab and pembrolizumab have been FDA approved only in patients with R/M HNSCC and who are refractory to platinum-based chemotherapy. If patient experiences disease progression on or after prior Platinum Based chemotherapy, patient should receive Immune Checkpoint Inhibitor monotherapy or be enrolled in an appropriate clinic trial. 2) Clinical trials, including those that are immunotherapy-based, should be considered in all HNSCC patients, in all lines of therapy