Jonathan Strosberg, MD
Findings from the phase III NETTER-1 trial led to the January 2018 FDA approval of Lutathera (lutetium Lu 177 dotatate) for the treatment of patients with somatostatin receptor–positive gastroenteropancreatic tumors (GEP-NETs). The trial compared Lutathera with high-dose octreotide LAR for patients with 1 or 2 metastatic midgut NETs.
In NETTER-1, patients with midgut NETs who progressed on 30 mg of octreotide were randomized to Lutathera (n = 116) or high-dose octreotide (n = 113). Patients received 4 doses of Lutathera at 7.4 GBq every 8 weeks in combination with 30 mg of octreotide. The control arm received 60 mg of octreotide LAR every 4 weeks.
In the study, there was a 79% reduction in the risk of progression or death with Lutathera compared with octreotide. The median progression-free survival (PFS) had not been reached in the Lutathera arm compared with 8.5 months in the high-dose octreotide arm (HR, 0.21; 95% CI, 0.13-0.32; P
The overall response rate with Lutathera was 13% versus 4% with octreotide (P
<.0148). At the interim analysis of overall survival (OS) there was a 48% reduction in the risk of death seen with Lutathera versus octreotide (HR, 0.52; 95% CI, 0.32-0.84).
Following the Luthathera approval, Jonathan R. Strosberg, MD, notes that challenges remain and ongoing studies are exploring more novel regimens and combinations.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Gastrointestinal Cancers, Jonathan R. Strosberg, MD, an associate professor of Moffitt Cancer Center, discussed ongoing advances and challenges in the treatment of patients with NETs.
OncLive: How has treatment for patients with NETs and carcinoid syndrome evolved over the past couple years?
It has been a pretty exciting couple of years in the treatment of NETs and carcinoid syndrome. We've had the approval of everolimus (Afinitor) a few years ago for the treatment of progressive NETs of the gastrointestinal (GI) tract and lungs. Last year, we saw the approval of telotristat ethyl (Xermelo), a serotonin inhibitor, for the treatment of diarrhea related to carcinoid syndrome. [Recently] Lutathera, a radiolabeled somatostatin analog, was approved for the treatment of patients with progressive GEP-NETs.
Can you explain the significance of the Lutathera approval?
Radiolabeled somatostatin analogs have been developed for the past several decades, primarily in Europe. They have been manufactured in hospitals and have treated thousands of patients. The principle is delivery of a radioactive somatostatin analog to a somatostatin receptor–expressing NET.
The results have been quite good, with response rates ranging from about 20% to as high as 50% in pancreatic NETs. Significant median PFS durations have also been reported. Though it took time for the phase III NETTER-1 trial to get regulatory approval, the results showed substantial improvement in PFS as well as strong evidence that OS is improved. In a few years, this will be re-examined with a mature analysis.
The European Medicines Agency approved Lutathera in September 2017, and the FDA approved it at the end of January not only for midgut tumors, but also in NETs of the stomach, pancreas, colon and rectum.
What should physicians keep in mind with regard to Lutathera’s safety and dosing schedule?
The standard regimen consists of 200 mCi of lutetium Lu 177 dotatate once every 8 weeks or so before treatment. It’s really 4 treatments over 8 months. The drug is often given combined with a somatostatin analog, either a long-acting octreotide or lanreotide, especially in patients with carcinoid syndrome.