Somatuline Depot is being explored for patients with lung neuroendocrine tumors.
Somatuline Depot (lanreotide), a somatostatin analog, has been giving select patients with gastroenteropancreatic neuroendocrine tumors (NETs) more treatment options, given the significant improvement in progression-free survival (PFS) demonstrated in this population since the drug’s approval in 2014.
Now, investigators are examining the potential that the agent could have in patients with lung NETs — an area that is greatly lacking in research — in a potentially practice-changing clinical trial that seeks to determine the role of the synthetic growth inhibitory hormone in patients with the rare tumor type. Thus far, no prospective trials specifically for patients with lung NETs have been reported, researchers have noted.
“Neuroendocrine tumors can start anywhere in the body,” said Diane Reidy-Lagunes, M.D. “The most common place is in the gastrointestinal [GI] tract, but they also strike very frequently in the lung. The truth is that we really haven’t paid much attention to lung NETs, and it really needs to be considered.”
Lagunes is the principal investigator on the SPINET trial—an international, phase 3, randomized, double-blind study evaluating the efficacy and safety of Somatuline Depot plus best supportive care compared with placebo plus best supportive care in patients with well-differentiated, metastatic and/or unresectable, typical or atypical lung NETs (NCT02683941).
“We are trying to get a really good understanding of whether somatostatin analogs work for lung NETS and, if they do, for how long?” Lagunes, a medical oncologist at Memorial Sloan Kettering Cancer Center, said in an interview with CURE. “It is an important study that can help us better understand the disease and then [better] help our patients.”
Lagunes said patients with lung NETs are frequently treated as though they have small cell lung cancer, another type of NET. “However, we know [the tumors] are completely different; they are different genetically and clinically,” she said. “Therefore, these patients should not be treated with platinum-based therapy up front and shouldn’t be treated with radiation.
“Our lung colleagues are [starting to] understand that now as well, but we just don’t have the data and the clinical trials in lung NETs to prove that they should be treated similar to GI nets,” Lagunes said. “These patients are not necessarily treated by neuroendocrine specialists; they’ve been treated by world-renowned lung cancer specialists—but they are two different diseases. That’s part of the problem.”
The SPINET trial has two phases: a double-blind phase during which patients are randomized two to one to receive Somatuline Depot versus placebo and an open-label period during which patients who already have received Somatuline Depot would continue therapy while those in the placebo arm would have the option to cross over to Somatuline Depot.
The primary analysis will occur during the double-blind phase of the trial, which will end when 175 progression or death events have been reached. Both parts of the open-label phase will end six months following the date of data cut-off. The primary endpoint of SPINET is PFS, which will be measured by central review every 12 weeks using RECIST v1.1 criteria. Secondary endpoints include overall survival, time-to-treatment failure, disease control rate, change in quality of life and objective response rate.
To be eligible for enrollment, patients with a typical carcinoid tumor must have a mitotic index of less than two mitoses/2 mm2 and patients with an atypical carcinoid must have less than 10 mitoses/2 mm2 and/or foci of necrosis. Tumors also must be somatostatin receptor—positive upon imaging.
Patients who need somatostatin analog therapy for symptom management and those who have received such treatment within six weeks of randomization will be excluded from the trial. Additionally, patients may not have undergone more than one course of chemotherapy for lung NETs at any time.
SPINET, which started in February 2016, is planned for an enrollment of 216 patients and is estimated to be completed by August 2019. Patients are accruing at 11 sites in the United States, with European sites scheduled to open, as well. Lagunes said that SPINET is “not a very large study,” but that it would be difficult to recruit patients because the tumor type is relatively rare. “This is why we are encouraging all physicians that if they do see a [patient with] a lung NET, to strongly consider referring them to major cancer centers to be able to discuss this trial and see if it’s appropriate for the patient we are addressing.”