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Head and Neck



80% of Head and Neck Squamous Cell Carcinoma (HNSCC) patients present advanced disease at diagnosis and, despite aggressive multimodal treatment regimens, the locoregional recurrence rate is about 50% in the first 5 years; noteworthy, about 10% of patients have metastatic disease at presentation. Once disease relapses, and is no longer amenable to locoregional curative treatment, prognosis worsens, with a 5 years survival rate that decreases from 50% to 15% and a median overall survival of 13 months. Given the results of recent phase 3 trial, systemic options as first line treatment are amplified, with the possibility of choice between pembrolizumab, pembrolizumab combined with chemotherapy, and chemotherapy combined with cetuximab. However, there is a lack of data regarding real world activity and efficacy of (chemio)immunotherapy, impact on quality of life, and on factors (such as biological age, symptoms burden …) that may contribute to the therapeutic choice.
The REALKEY study is a prospective, observational study that aims to describe a real world cohort data of recurrent or metastatic HNSCC patients treated with systemic treatment (either immunotherapy, or chemo-immunotherapy or chemotherapy + cetuximab).

Selection criteria

Main selection criteria are:
– Histological diagnosis of recurrent and/or metastatic HNSCC, not amenable for curative locoregional treatment (either surgery or radiotherapy), and amenable for first line systemic treatment
– Patients who received any oncological systemic treatment for HNSCC, outside from treatment with curative intent (e.g cisplatin concomitant with radiotherapy as definitive or adjuvant setting) are not allowed.


The primary objective of the study is to describe a cohort of patients with RM HNSCC tumors not eligible for surgery or curative radiotherapy, otherwise eligible for systemic treatment as first-line therapy, in terms of treatment choice, PDL1 CPS score assessment, and outcome. Secondary objectives are to evaluate systemic treatment activity in terms of response rate (at first and second line systemic therapy), efficacy in terms of overall survival, progression-free survival, and progression free survival at second line treatment (PFS 2), safety in terms of CTCAE v5.0, prediction of treatment toxicities according to G8 questionnaire (limited to patients aged more than 70 years old), prognostic/predictive role of biochemical, clinical and pathological parameters, and change in quality of life (EORTC QLQ C30/HN43). Moreover the trial aims to create a repository of radiological and histological specimens for future radiomic and translational analysis.

Participating centers