Durable intracranial and extracranial response to nivolumab with appearance of secondary resistance in a heavily pretreated patient with head and neck cancer.
BACKGROUND
Recently, nivolumab was approved in the second-line setting of squamous cell cancer of the head and neck (SCCHN). The benefits of PD-(L)1 inhibitors in PD-L1(-) tumors are unclear, and no reports exist on the activity of these agents in brain metastases from SCCHN. Little is known regarding the mechanisms underlying acquired resistance to PD-(L)1 inhibition.


METHODS
A patient with PD-L1(-) metastatic SCCHN progressing to cetuximab-based chemotherapy received third-line nivolumab. T cell infiltration and mRNA expression of immune-related genes were compared in prenivolumab and postnivolumab biopsies from a progressing tumor lesion.


RESULTS
An exceptional local and systemic response was achieved, including complete devitalization of brain metastases that lasted for more than a year. Increased T cell infiltration and upregulation of genes related to T cell exhaustion and resistance to PD-1 inhibition were found.


CONCLUSION
Durable responses to PD-(L)1 inhibitors may be observed in biomarker-negative SCCHN. Mechanisms of resistance should be studied.
['Cabezas-Camarero|Santiago|S|0000-0003-2298-8577', 'García-Barberán|Vanesa|V|', 'Sáiz-Pardo Sanz|Melchor|M|', 'Cabrera-Martín|María Nieves|MN|', 'Gimeno-Hernández|Jesús|J|', 'Pérez-Segura|Pedro|P|']
D000074322:Antineoplastic Agents, Immunological D002294:Carcinoma, Squamous Cell D059248:Chemoradiotherapy D000073496:Frailty D006258:Head and Neck Neoplasms D006801:Humans D008297:Male D008875:Middle Aged D009362:Neoplasm Metastasis D000077594:Nivolumab D061026:Programmed Cell Death 1 Receptor
nivolumab head and neck cancer brain metastases acquired resistance PD-L1 cetuximab