Sapanisertib for Neuroendocrine Tumors

The signs of neuroendocrine neoplasia include Cushing's or Nelson's syndrome and Cushing syndrome. Abdominal bloating, loss of appetite, weight loss, peripheral edema and edema of the hands or feet are the cardinal symptoms of cirrhosis.\n

Patients with neuroendocrine tumors in the United States tend to be younger than those diagnosed in other countries. Patients with neuroendocrine tumors appear to have a higher prevalence of nonfunctional tumors and lower prevalence of hyperfunctioning tumors. Patients with neuroendocrine tumors tended to have more aggressive diagnoses and higher recurrence rates.

Local and whole-organ recurrence rate is very high after surgical resection for NET. The role of imaging and surgical methods is not clearly defined. Most studies have revealed that the overall survival of patients with NET is not different when compared with that without NET.

Symptoms are managed with symptomatic drugs (selective serotonin receptor-3 agonists, selective serotonin reuptake inhibitors, and antiandrogens) or nonselective drugs (procedural sedation or tricyclic antidepressant augmentation) to reduce high levels of circulating or tissue serotonin or by blocking 5-HT3R with ondansetron alone or compounded with 5-HT antagonists. Treatments are typically given in combination. Other pharmacologic treatments used for neuroendocrine tumors include 5-HT3R antagonist ondansetron alone or combined with 5-HT antagonists, and/or opioid agonists and antagonists. The treatment of choice for the majority of cases remains undefined.

Neuroendocrine tumors are caused by factors as diverse as genetic mutations, diet, hormones, radiation, and infections. The most common location for neuroendocrine tumors is the gastrointestinal tract. There is not a single cause.

Neuroendocrine tumors are cancerous (cancerous) tumors which usually originate in one of the endocrine glands, particularly the pancreas, that produce hormones (such as insulin or growth hormone). They are often called "islet cell tumors". Most cases of neuroendocrine tumors are associated with a condition called acromegaly. Patients with neuroendocrine tumors most often develop symptoms associated with this condition.\n

Considering the magnitude of the anticipated toxicities of sapanisertib, patients who are elderly, have a poor renal function or have a history of renal impairment may be at risks for sapanisertib-related adverse events. The risks for most other commonly expected adverse events are expected to be low.

There is currently very limited evidence supporting the use of neuroendocrine tumors with [SURGIC] if the patient has a good performance status(<80) and cannot get chemotherapy.

For a better understanding concerning the efficacy and safety as well as the optimal dosage and scheduling of sapanisertib, a large, ongoing, multicentre trial is planned.

Results from a recent paper demonstrated the superiority of pan-HER inhibitor sapanisertib (dasatinib) over a placebo in patients with advanced/metastatic HER2-overexpressing breast or GI carcinomas. Because no other TKIs were studied in this population, we conclude that other targeted approaches may result in greater efficacy in HER2+ breast or gastro-oesophageal carcinoma.

In a retrospective review, sapanisertib significantly improved QOL for patients with NETs as measured by PSAV, the EORTC QOL questionnaire, and patient-reported distress. In a recent study, findings suggest that the effect of sapanisertib is not limited to tumor shrinkage and should be considered when evaluating the efficacy of new anticancer drugs.