ICI therapy safe to use in aggressive pituitary neuroendocrine tumours

Treatment with immune checkpoint inhibitors (ICI) is safe and feasible in patients with aggressive pituitary neuroendocrine tumours (PNTs), a recent study has shown.

“We also identified mismatch repair deficiency (MMRd) and temozolomide hypermutation as potential biomarkers of response to ICI,” the investigators said.

A single-centre, prospective, phase II trial was performed to examine the activity of ipilimumab and nivolumab in patients with PNTs. Objective response using the iRANO response criteria served as the primary endpoint. The investigators also explored genetic biomarkers of response to ICIs in 13 patients who received ICIs on or outside of this study.

Of the 10 patients with PNTs who met the eligibility criteria, five had corticotroph, four had lactotroph, and one had somatotroph tumour. Nine out of 10 participants (four metastatic and five nonmetastatic) were evaluable for the primary endpoint.

No objective responses were noted, but tumour shrunk in two of nine patients. In a biomarker discovery cohort involving seven tumours treated on trial and six treated off trial, immunological response was found to be significantly associated with MMRd and temozolomide hypermutation.

Of note, evidence of immunoediting, characterized by loss of MMRd and/or a decrease in tumour mutational burden was identified in three tumours sequenced pre- and post-ICI treatment.

“Overall, our data suggest that ICIs might provide an additional treatment option for PNT,” the investigators said. “This should be evaluated more broadly in future studies.”