Endocrine Abstracts

Aggressive pituitary tumours (APT) are not controlled by standard therapies. Pituitary carcinomas (PC) share many properties with APT and are defined by the presence of metastases. Temozolomide (TMZ), an oral alkylating with good penetrance into the brain, is the recommended first line chemotherapy. The survival has markedly been improved in patients with APT/PC during the last two decades. Prior to the TMZ-era, 66% of patients with PC were dead within a year after detection of metastases, today the median survival is about 5 years. TMZ results in tumour regression in 40% of patients. The TMZ effect can be counteracted by the DNA repair enzyme MGMT; complete tumour regression has only been observed in tumours with low MGMT content. TMZ is considered to be a radiosensitizer and is given concurrently with radiotherapy in malignant glioblastomas. In APT /PC this combination may be superior to TMZ monotherapy, but the experience is limited. Management remains challenging in TMZ failures and relapsing tumours. A second radiotherapy had transient effects in about 40% of 55 re-irradiated patients. Peptide Receptor Radionuclide Therapy has resulted in partial tumour regression in 4 of 19 evaluable patients. Targeted therapies interfering with growth factor receptors on tumour cells (tyrosine kinase inhibitors) or intracellular signaling pathways (mTor inhibitors), reported in 11 cases, have mostly been unsuccessful. Bevacizumab is a monoclonal which blocks binding of VEGF to its cell surface receptor. Of 12 patients treated with bevacizumab monotherapy, 2 achieved a partial response and 6 tumor stabilization. Treatment with immune checkpoint inhibitors seems promising with complete response in 1 and partial regression in 7 (9) of 29 treated patients. There is no clear difference between the effects of PD-1 blockers and dual inhibitors (anti-CTLA-4 + anti-PD-1). Biomarkers for selecting patients who will benefit from ICI remain to be identified.