Durable intracranial and extracranial response to nivolumab with appearance of secondary resistance in a heavily pretreated patient with head and neck cancer

Abstract

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.

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