The Impact of Locoregional Treatment on Response to Nivolumab in Advanced Platinum Refractory Head and Neck Cancer: The Need Trial

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.

Durable complete response rates following radiotherapy and immunotherapy combination in recurrent and metastatic head and neck squamous cell carcinoma: A retrospective single‐centre cohort study

“…However, defining the optimal dose of radiotherapy and the context of previous irradiation may be critical in determining the immune response. 8 There is a clear need for improved predictors of response to immunotherapy. It may be hypothesised that response to radiotherapy and immunotherapy combination may be associated with expression of the Programmed Death-1 Receptor Ligand (PD-L1).…”

“…Also, in the current study, the dose of radiotherapy varied between patients and was determined as per standard of care. However, defining the optimal dose of radiotherapy and the context of previous irradiation may be critical in determining the immune response 8 …”

Combining radiotherapy and immunotherapy in definitive treatment of head and neck squamous cell carcinoma: review of current clinical trials

“…85,86 Furthermore, clinical data show reduced efficacy of anti-PD-1 in previously treated patients with HNSCC. 87 This speaks strongly in favour of using an immunoradiotherapy combination before surgery as compared to its postoperative application. Neoadjuvant RT is not considered a standard of care in HNSCC, therefore these "window of opportunity trials" serve mostly to advance our understanding of the underlying mechanisms and to lay the ground for further studies.…”

“…Considering only non-cancer/TME-related factors, synergism between anti-PD-1 and RT is probably most pronounced when these two treatment modalities are delivered concurrently in previously untreated patients with intact draining lymph nodes and no lymphopenia. [85][86][87][95][96][97][98] Definitive immunoradiotherapy as a sole treatment fulfils these criteria, except for nodal irradiation. If, in a neoadjuvant setting, elective nodal irradiation is not mandatory, its omission would be ill-advised in a definitive (chemo)radiotherapy setting based on our current knowledge.…”

The Role of Opioids in Cancer Response to Immunotherapy

“…Several studies will aim to understand which mechanisms, factors or tumor' pathways generate inherently or acquired resistance to cancer immunotherapies [15]. Response to ICIs can be in uenced by several factors: the molecular pro le of cancer [16][17][18][19], histopathological features of tumor [20][21][22] and clinical characteristics of patient, such as site of metastases [23,24], Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [25,26], previous treatments [27][28][29][30] or external intervention such as drug interactions with immune system [31]. While corticosteroids and antibiotics are already known to have an immunomodulatory effect [32][33][34], less well known is the effect of concomitant opioids therapy used in symptomatic patients for the treatment of uncontrolled pain [35].…”