Abstract
Background: Previous locoregional treatment could affect the response to nivolumab in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). The aim of this study is to evaluate the impact of the clinicopathological characteristics and previous treatment in predicting early progression to nivolumab in a real-world population. Methods: This is an observational, multicenter retrospective/prospective study including patients (pts) with platinum refractory R/M HNSCC who received nivolumab 240 mg every 2 weeks from October 2018 to October 2019. We analyzed the association between previous treatment, clinicopathological characteristics, and early progression (within 3 months). Results: Data from 61 pts were reviewed. Median age was 67 years (30–82). Forty-two pts (69%) received previous locoregional treatment. Early progression to nivolumab occurred in 36 pts (59%), while clinical benefit (stable disease and partial response) was achieved in 25 pts (41%). Early progression to nivolumab was significantly associated to previous locoregional treatment both at univariate and multivariate analysis (p = 0.005 and p = 0.048, respectively). Conclusion: nivolumab in R/M HNSCC is burdened with a high early progression rate. Previous wide neck dissection and high dose radiotherapy may compromise the efficacy of nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response.
Highlights
Head and neck cancer represents the sixth most common type of neoplasia worldwide with650,000 new cases and around 330,000 deaths each year [1]
Radical surgery with the demolition of the complex lymphatic network of the neck associated with adjuvant high dose radio-chemotherapy or primary radio-chemotherapy, carried out for reducing local recurrence and improve disease control, radically modify the anatomy of the local lymphatic system, hindering the priming of immune response (Figure 2)
The first postoperative phase is characterized by the increase of cytokines of wound healing, programmed death ligand-1 (PD-L1) expression, myeloid-derived is characterized by the increase of cytokines of wound healing, PD-L1 expression, myeloid-derived suppressor cells (MDSC), macrophages M2, and Treg
Summary
Head and neck cancer represents the sixth most common type of neoplasia worldwide with650,000 new cases and around 330,000 deaths each year [1]. The vast majority (more than 90%) of head and neck cancer are squamous cell carcinoma arising from various subsites of the upper aerodigestive tract. These cancers are strongly associated to specific risk factors such as tobacco and alcohol intake and human papilloma virus (HPV) infection, the latter defining a distinct disease entity [2]. In the pre-immunotherapy era, the diagnosis of unresectable recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) was linked to an invariably poor prognosis with an expected survival of less than 1 year [3]. Previous locoregional treatment could affect the response to nivolumab in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Previous wide neck dissection and high dose radiotherapy may compromise the efficacy of nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response
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