Abstract
Simple SummaryImmunotherapy has made a breakthrough in the treatment of patients with recurrent and/or metastatic head and neck squamous cell carcinoma in the second line setting with anti-PD-1/PD-L1 immune checkpoint inhibitors. Furthermore, the KEYNOTE-048 study has established a new standard of care with immunotherapy in the first line setting, leading to a paradigm change for the treatment of patients with recurrent and/or metastatic head and neck squamous cell carcinoma. No study since 2008 could demonstrate an improvement in survival of these patients until the publication of the KEYNOTE-048 study. Here we will decipher this new paradigm in the first-line line setting and discuss associated challenges.Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) in combination with platinum-based chemotherapy has been for the decade standard of care for the treatment of head and neck squamous cell carcinomas (HNSCC) patients in the first-line recurrent and/or metastatic setting. The KEYNOTE-048 trial published last year established a new paradigm in this setting with the demonstration that immunotherapy should be given either alone or in combination with chemotherapy. Indeed, pembrolizumab, an antiprogrammed cell death 1 (PD-1) immune checkpoint inhibitor, improved overall survival as compared to the EXTREME regimen in patients expressing PD-L1 in the tumor microenvironment, which represents a large majority of the patient population. In this review, we will decipher this important change of paradigm in the first-line treatment of recurrent and/or metastatic HNSCC, and discuss associated challenges.
Highlights
Head and neck cancers accounted for approximately 890,000 new cases and 450,000 deaths worldwide in 2018, representing the seventh most frequent cancer worldwide [1].Squamous cell carcinoma is the most frequent histological subtype of head and neck cancers, beside other rare histological types
It seems important to take into account the kinetic of disease progression, and whether or not the patient presents with symptomatic and/or life-threatening tumor localization, as it might require rapid tumor shrinkage and may lead clinicians to prefer the combination of pembrolizumab with chemotherapy, if patient is fit for platinum-based chemotherapy
The phase 3 KEYNOTE-048 has been the first study to change the standard of care for the treatment of patients with recurrent and/or metastatic head and neck squamous cell carcinomas (HNSCC) in the first-line setting since 2008 after the publication of the EXTREME study
Summary
Head and neck cancers accounted for approximately 890,000 new cases and 450,000 deaths worldwide in 2018, representing the seventh most frequent cancer worldwide [1]. Squamous cell carcinoma is the most frequent histological subtype of head and neck cancers, beside other rare histological types. Diagnosis and multimodal treatments, recurrent and/or metastatic head and neck squamous cell carcinomas (HNSCC) develop in approximately 50% of patients with locally advanced HNSCC [3]. In 2008, the EXTREME phase 3 study was the first study in 30 years to demonstrate an improved disease control and OS in the first-line setting in patients with recurrent and/or metastatic HNSCC, with the addition of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) to platinum-based chemotherapy versus chemotherapy alone [5]. We will describe the current standards in the first-line treatment for patients with recurrent and/or metastatic HNSCC, with an extensive presentation of immunotherapy data in this setting. Standard Treatments before the Era of Immunotherapy for Patients with Recurrent and/or Metastatic HNSCC
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