A Revolution in the Treatment of Neuroendocrine Tumors

Patients with neuroendocrine tumors have more treatment options than ever before.
An even more detailed imaging test became available in June 2016, when the FDA approved a new diagnostic agent for positron emission tomography (PET) scans called gallium 68 Ga-Dotatate. The product, which has the brand name Netspot,is a radioactive tracer that binds to receptors for somatostatin, producing scans that show exactly where NETs are and how likely they are to respond to therapies that target the receptors.

Because gallium 68 Ga-Dotatate binds to somatostatin receptors, it reflects the density of such receptors, which can not only help predict how patients will respond to somatostatin analogs but also aid surgeons in deciding on the proper course for surgery. “This new type of PET scan allows you to detect smaller lesions, which helps you make a decision about whether you can operate for a cure or not,” Yao says.

Emerging Targeted Treatments

Several targeted treatments for NETs are being developed. In February 2016, the FDA approved the chemotherapy drug, Afinitor (everolimus), for patients with advanced or metastatic gastrointestinal or lung NETs who aren’t eligible for surgery.

Afinitor blocks mTOR, a proteinsignaling pathway that can malfunction and contribute to the growth of some cancers. In a pivotal trial, the drug increased median PFS by seven months in patients with advanced GI or lung NETs.

Now Afinitor is being tried in combination with LEE011 (robciclib), an experimental drug that inhibits two proteins called cyclin-dependent kinase 4 and 6 (CDK 4/6). These proteins also enable the growth of cancer cells. “The idea is that we’re trying to target the mTOR pathway with two different drug mechanisms,” says Diane Reidy-Lagunes, M.D., a medical oncologist at Memorial Sloan Kettering Cancer Center (MSK) in New York City and the lead investigator for a phase 2 trial, which is recruiting patients with NETs in the foregut. When the combination was initially tested in cells from pancreatic NETs, she adds, the results indicated that the approach “could be very promising.”

Another emerging treatment that oncologists are watching is a variation of the Netspot imaging system that uses somatostatin analogs to deliver radiation directly to tumors. Lutathera (lutetium Lu 177 dotatate) falls under the PRRT umbrella, a new class of treatments. In a phase 3 trial of patients with GI NETs, Lutathera reduced the risk of disease progression or death by 79 percent versus treatment with octreotide.

“In many patients, PRRT is highly effective,” says Thomas O’Dorisio, M.D., a professor and endocrinologist at the University of Iowa Hospitals & Clinics, who has been an investigator for several clinical trials. Response to the therapy, he adds, “has to do with the quality and number of [somatostatin] receptors on the tumors,” which has become easier to evaluate thanks to improved imaging technology. “We’re getting to the point where we can predict effectiveness based on a gallium scan before treatment.”

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