SUN-064 - Sustained Progression-Free Survival after 2 Years of Immune Checkpoint Inhibitor Therapy in A Patient with Metastatic Pituitary Carcinoma

Introduction
Aggressive pituitary adenomas are a rare subset of pituitary neuroendocrine tumors (PitNETs), with a small percentage progressing to metastatic pituitary carcinoma (PC). The European Society of Endocrinology recommends temozolomide (TMZ) as first line chemotherapy and consideration of immune checkpoint inhibitors in patients with rapid tumor progression not responsive to surgery or radiation. There are limited cases describing ipilimumab/nivolumab dual therapy followed by nivolumab maintenance. This case describes a patient with PC who received nivolumab maintenance for over 2 years with minimal side effects and remains progression-free.

Case Description
A 65-year-old male with hypertension and type 2 diabetes presented to endocrinology clinic to establish care for ongoing treatment of metastatic PC.
At initial presentation 10 years ago, the patient was diagnosed with Cushing disease and underwent surgical resection of an invasive 10 mm pituitary corticotroph adenoma. Within a year, the adenoma recurred and the patient underwent a second surgery followed by sellar radiation. Due to rising ACTH >1000 pg/mL and ongoing hypercortisolism, he was trialed on cabergoline and mifepristone, but the latter was complicated by severe hypokalemia, and he underwent bilateral adrenalectomy. DOTATATE PET imaging soon after demonstrated widely metastatic tracer-avid osseous lesions, later confirmed on bone biopsy as PC. He received pasireotide twice daily for one month and then transitioned to TMZ.
For over two years, the patient underwent 11 cycles of TMZ with seemingly stable disease on DOTATATE imaging but no improvement of ACTH levels. Subsequent FDG PET scan showed disease progression with lytic skeletal lesions and new avid hilar and celiac lymph nodes. The patient then began four cycles of ipilimumab/nivolumab every 3 weeks with downtrending ACTH levels. Skin hyperpigmentation rapidly resolved. He went on to complete three more cycles of nivolumab alone every two weeks, followed by two years of maintenance nivolumab every four weeks. Surveillance FDG PET scans currently show no evidence of recurrence, and ACTH levels remain low. Given the long duration of immunotherapy and apparent remission of his PC, nivolumab was stopped with plan for close monitoring of ACTH every 3 months.

Discussion
This case demonstrates over two years of progression-free survival on nivolumab in a patient with widely metastatic PC, notably with minimal side effects, in which TMZ was not effective for disease control. Additionally, this case highlights the importance of utilizing FDG versus DOTATATE imaging when monitoring patients with aggressive PitNETs that lose somatostatin receptor positivity, as his disease progression was likely missed on repeat DOTATATE scans. Optimal timing of immunotherapy initiation and duration of use warrant further study in the management of PC.

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