Approximately 50% of melanomas harbor an activating BRAF mutation. Combined BRAF and MEK inhibitors such as dabrafenib and trametinib, vemurafenib and cobimetinib, and encorafenib and binimetinib are US Food and Drug Administration (FDA)-approved to treat patients with BRAFV600-mutated advanced melanoma. Both genetic and epigenetic alterations play a major role in resistance to BRAF inhibitors by reactivation of the MAPK and/or the PI3K–Akt pathways. The role of BRAF inhibitors in modulating the immunomicroenvironment and perhaps enhancing the efficacy of checkpoint inhibitors is gaining interest. This article provides a comprehensive review of mechanisms of resistance to BRAF and MEK inhibitors in melanoma and summarizes landmark trials that led to the FDA approval of BRAF and MEK inhibitors in metastatic melanoma.

This article is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The guidelines panel consisted of medical oncologists, pathologists, gastroenterologists, endocrinologists, and radiologists. The panel reviewed a series of questions regarding the medical management of patients with pancreatic neuroendocrine tumors as well as questions regarding surveillance after resection. The available literature was reviewed for each of the question and panel members voted on controversial topics, and the recommendations were included in a document circulated to all panel members for a final approval.

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Objectives The objective of this study was to describe the outcomes of patients in the University of Iowa (UI) Neuroendocrine Tumor (NET) Database treated with peptide receptor radionuclide therapy (PRRT). Methods 135 patients from the UI NET Database who received PRRT were analyzed, their characteristics described and survival calculated. Results The median age at diagnosis was 51 years and 64% were men. The primary tumor was located in the small bowel (SBNET) in 37.8%, the pancreas (PNET) in 26.0%, the lung in13.3%, unknown primary in 9.6%, and other sites in 13.3 %. A radiographic response of any magnitude was observed in 65.8%, 11.1% had a mixed response, and 15.4% showed progression. The overall survival (OS) from first PRRT was 40 months and the median time to progression (TTP) was 23.9 months. Higher pre-treatment chromogranin A and pancreastatin levels predicted inferior OS. Conclusions PRRT resulted in a relatively long OS and TTP in heavily pretreated North American patients with advanced NETs. Elevated pre-treatment chromogranin A and pancreastatin predicted shorter OS after therapy. PRRT is a valuable treatment options in patients with advanced NETs, especially SBNETS.