Chemoradiotherapy plus a SMAC mimetic for locally advanced squamous cell carcinoma of the head and neck
Mené en France et en Suisse sur 96 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade locorégionalement avancé (âge : 18 à 75 ans ; durée médiane de suivi : 25 mois), cet essai randomisé de phase II évalue l'efficacité, du point de vue du contrôle locorégional de la maladie 18 mois après le traitement, et la toxicité du Debio 1143, un nouvel antagoniste oral des protéines inhibitrices de l'apoptose, en combinaison avec une chimioradiothérapie standard comportant une dose élevée de cisplatine
The availability of checkpoint inhibitors has led to substantial progress in the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck. For locoregionally advanced disease, a potentially curable condition, concomitant chemotherapy and radiotherapy (chemoradiotherapy) has remained the mainstay of organ-sparing treatment. However, the treatment outcome of locoregionally advanced squamous cell carcinoma of the head and neck, traditionally associated with alcohol and nicotine consumption, still remains poor. A notable exception is human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma, which represents a distinct disease entity with a more favourable prognosis. Although various regimens are used in daily clinical practice, high-dose cisplatin chemoradiotherapy is considered to be the standard of care and the most effective chemoradiotherapy regimen in terms of oncological outcome. In this regard, HPV-positive locoregionally advanced oropharyngeal squamous cell carcinoma is no exception, as was recently demonstrated in two randomised trials. Serious treatment-related toxicity resulting from high-dose cisplatin chemoradiotherapy, both acute and chronic, is common, and appropriate patient selection for this treatment is crucial. Additionally, disease recurrence following chemoradiotherapy is prevalent, especially for patients with high-risk HPV-negative squamous cell carcinoma of the head and neck. Upon relapse, prognosis is generally poor because salvage treatment options are often scarce. Therefore, the need for more effective treatment regimens remains.