Systemic therapy options for NETS: When and what


Session type:

Ramon Salazar1
1Institut Català d’Oncologia, L´Hospitalet de Llobregat, Barcelona, Spain


Well-differentiated NETs (WDNETs) are a subset of tumours with slow growth and sometimes relatively indolent behaviour. STZ based chemotherapy has been the only standard systemic therapy for pancreatic NETs (pNETs) for decades.

Recently the mTOR inhibitor, everolimus, has shown to be efficacious in well differentiated NETs. Everolimus 10mg/day, as compared with placebo, significantly prolonged progression-free survival among patients with progressive advanced pancreatic neuroendocrine tumours and was associated with a low rate of severe adverse events (RADIANT-3 study). Results published from this study showed a median progression-free survival of 11.0 months. This study included patients with advanced, low-grade or intermediate grade pNET with radiologic progression within the previous 12 months. Sinchronously, sunitinib has shown simillar results in the same population. Patient characteristics, safety profile, final sample size and conduct of the trial design and statistics differ between trials but both drugs have been recently approved for its use in advanced pNETs in the US by the FDA and in Europe by the EMEA.

STZ-5-FU is the current standard of care for advanced pNETs in the European Union (ENETS guidelines; Neuroendocrinology 2012). Everolimus and sunitinib are also available and reimbursed in many countries for the same population. One can speculate on a number of clinical variables that may help guide the right treatment sequence and these will be reviewed but the lack of valid predictors of response for one or another drug makes it impossible to choose the optimal sequence for every patitent. A randomised study is needed to have a clear knowledge about the best sequence of administration of these new targeted thrapies and chemotherapy. A concept and design for such a trial is underway and will be presented. The SEQTOR trial aims to randomise patients with advanced pancreatic pNETs to receive STZ-5FU chemotherapy upfront and everolimus upon progression or the inverse sequence. In addition, a large ancilliary biologic study exploring putative predictive and monitoring biomarkers will also be performed, with the idea to find specific biomarkers of response that may help individualise treatment decission in the future.