Endocrine Abstracts

Introduction: Metastatic pituitary neuroendocrine tumors (PitNETs) or pituitary carcinomas are rare and challenging conditions. We present a recent and encouraging observation of a temozolomide (TMZ)-resistant clinically non-functioning metastatic PitNET showing a remarkable response to the anti-PDL1 drug Pembrolizumab.

Case presentation: A 57-years-old man had transsphenoidal surgery in November 2012 for a large non-functioning intra/suprasellar mass revealed by visual defects, and invasive into the left cavernous sinus. A diagnosis of “null cell” PitNET (Ki-67 10%, p53 5%) was made and in June 2013 the surgical resection was completed transcranially. One year later he received stereotactic radiotherapy on the left cavernous remnant with a good response. However, delayed infrasellar regrowth was observed, first presenting as nasal pseudopolyps and leading to re-operation in March 2018. The pathological diagnosis was consistent with the aggressive clinical behavior (Ki67 20%, p53 10%) and two small pre-pontine nodules revealed metastatic progression. Further immunohistochemical characterization of the tumor indicated a PIT1 lineage. The patient started TMZ with a standard schedule for 5 cycles, followed by a metronomic schedule in association with stereotactic radiotherapy on pre-pontine nodules and additional small multiple asymptomatic brain and spinal metastases indicative of disease progression. The primary tumor also progressed with nasal obstruction and visual loss. Searching for alternative therapeutic options, a high expression of PDL-1 was found and suggested immunotherapy. TMZ was withdrawn and in March 2021 the patient started Pembrolizumab. Encouraging results were noticed after 4 cycles of treatment. After 8 cycles of treatment, a remarkable clinical, radiological and metabolic response was documented, with a significant shrinkage of the primary lesion, a regression of metastatic nodules, and a decrease of SUV values at 18-FDG PET-CT. Moderate cutaneous and renal toxicities (G1-G2) and mild eosinophilia were observed and successfully managed by systemic steroid therapy and transient drug withdrawal. Pembrolizumab is currently continued as a maintenance therapy.

Discussion: To the best of our knowledge, no such remarkable response to anti-PDL1 monotherapy in a Pit1-positive metastatic PitNET has been reported so far. Interestingly, in few reports of other aggressive or metastatic PitNET treated by immunotherapy, PDL-1 expression – if available - was low (<1%) or negative. This case supports recent data suggesting that PIT1-positive PitNETs may express more PDL-1 than other phenotypes.

Conclusion: This observation suggests a promising role of immunotherapy for metastatic PitNETs, refractory to standard therapy. In addition to the potential role of PDL-1 expression, further predictors of response should be searched for.