Abstract
Simple SummaryHead and neck squamous cell carcinoma (HNSCC), in the locally advanced setting, relapses in more than 50% of cases after surgery and/or chemo-radiotherapy. Prognosis is then very poor with platinum-based chemotherapy yielding a median survival of 10 months and a 2-year survival rate of less than 20%. In recent years, immunotherapy, has changed treatment and prognosis of several tumor types. Given their inflammatory profile and high mutational burden, HNSCC is a good candidate for immunotherapy. This review describes the major therapeutic breakthrough worked by Immune Checkpoint Inhibitors (ICIs) blocking the PD-1/PD-L1 axis. These monoclonal antibodies have doubled the 2-year survival rate thanks to long lasting responses with a favorable toxicity profile. Further progress is expected with new immunotherapeutic agents having a different mechanism of action combined with anti-PD(L)1, chemotherapy or targeted therapies.Head and neck squamous cell carcinoma (HNSCC) in the recurrent or metastatic (R/M) setting is a devastating disease with a poor prognosis. Until recently, the reference first line treatment was the EXTREME protocol, which yields a 10.1 months median survival, and almost no effective treatment are available in second line. Immune checkpoint inhibitors (ICIs) have changed the prognosis of several metastatic solid tumors. Given their inflammatory profile and high mutational burden, HNSCC is a good candidate for ICIs treatments. First, a strong pembrolizumab efficacy signal was shown in the Keynote-012 Phase Ib study. Then, the phase III Checkmate-141 study validated the efficacy of nivolumab in platinum-resistant patients. Finally, the first line conquest is acquired since the final results of the keynote-048 phase III study that demonstrated the superiority of pembrolizumab versus EXTREME in CPS ≥ 1 patients, and with the addition of platinum and 5FU in all patients. However, the first line treatment landscape is not frozen. Two studies (Checkmate-651 and Kestrel) are investigating the efficacy of the combination of antibodies raised against CTLA-4 and PD-(L)1. Results are impatiently awaited. Further progress needs the use of new immunotherapeutic agents such as monalizumab or ICOS agonist rather in combination with an anti-PD(L)1. New associations of ICIs and chemotherapeutic or targeted therapeutic agents are also actively investigated. Finally, ICIs has to be studied in the locally advanced setting where there is a chance of cure. Several trials are testing the potential synergistic combination of ICIs with radiotherapy and platinum or cetuximab, or ICIs used in a neoadjuvant setting.
Highlights
Head and neck squamous cell carcinoma (HNSCC) in the recurrent or metastatic (R/M) setting has a poor prognosis
Phase III studies have demonstrated the superiority for patient previously treated with platinum at first of Nivolumab (CHECKMATE-141 study) and later of pembrolizumab (KEYNOTE-040 study) versus standard of care (SoC), which resulted in an approval by the FDA at first and by the EMA later restricted to patients tumor proportion score (TPS) ≥ 50% for pembrolizumab
KEYNOTE-048 is the first immunotherapy in first line study in the treatment of R/M HNSCC to publish its results: this study is positive in overall survival for combined positive score (CPS) ≥ 1 patient with pembrolizumab alone and for the entire population with pembrolizumab + chemotherapy vs. EXTREME emerging as the new standard of care
Summary
Head and neck squamous cell carcinoma (HNSCC) in the recurrent or metastatic (R/M) setting has a poor prognosis. Until recently the EXTREME regimen had been the standard of care for patients considered as platinum-sensitive with a median survival of 10.1 months [1]. For patients pretreated with platinum, second line options are few (typically: methotrexate, cetuximab or taxanes) with a response rate that varies between 3% and 13% and a median survival inferior to 6 months [2,3,4]. HNSCC are frequently characterized by an inflammatory tumor profile with lymphocytic infiltration and a strong. PD-L1 expression on tumor cells and on tumor micro-environment (TME) cells alike In such tumors, lymphocytes, T helpers, induce the secretion of gamma interferon which stimulates the expression of PD-L1 on the TME cells protecting tumor cells from the action of cytotoxic T cells. Preclinical studies have shown that blocking the interaction between PD-1 and its ligand PD-L1 increases the activation of cytotoxic T cells and inhibits tumor growth [5]
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