Synergism of Checkpoint Inhibitors and Peptide Receptor Radionuclide Therapy in the Treatment of Pituitary Carcinoma

Abstract

Context: Aggressive pituitary tumors that have progressed following temozolomide have limited treatment options. Peptide receptor radionuclide therapy and immunotherapy may have a complementary role in the management of these tumors.

Methods: We provide follow-up data on a previously reported patient with a hypermutated recurrent tumor. The patient in this report provided written informed consent for tumor sequencing and review of medical records on an institutional review board-approved research protocol (NCT01775072).

Results: This patient with a corticotroph pituitary carcinoma with alkylator-induced somatic hypermutation has remained on treatment with ipilimumab and nivolumab for 3.5 years and remains clinically well. After an initial partial response to checkpoint inhibitors, she has had several recurrences that have undergone immunoediting of subclonal mutations, which have been effectively treated with continuation of immunotherapy, surgery, external beam radiation, and ¹⁷⁷Lu-DOTATATE. Following external beam radiotherapy (RT), she had radiographic evidence of an abscopal response at a distant site of disease suggesting a synergism between checkpoint inhibitors and RT. Following treatment with ¹⁷⁷Lu-DOTATATE, the patient had a partial response with a 61% reduction in volume of the target lesion.

Conclusion: In patients with aggressive pituitary tumors, treatment with checkpoint inhibitors may trigger an abscopal response from RT. With appropriate selection, an additional efficacious treatment, ¹⁷⁷Lu-DOTATATE, may be available for a limited number of patients with aggressive pituitary tumors, including patients who have progressed on temozolomide and exhibit increased somatostatin receptor expression on ⁶⁸Ga-DOTATATE positron emission tomography.

Keywords: PRRT; checkpoint inhibitor; immunotherapy; pituitary carcinoma.