Lanreotide (Somatuline Depot) improved progression-free survival and resulted in more disease control compared with an observation strategy among patients with pancreatic neuroendocrine tumors (pNETs).
Alexandria Phan, MD
Lanreotide (Somatuline Depot) improved progression-free survival and resulted in more disease control compared with an observation strategy among patients with pancreatic neuroendocrine tumors (pNETs) in a planned subgroup analysis of the CLARINET trial, which led to the FDA’s recent approval of the agent.
The findings support the results observed in the CLARINET trial in a broader patient population with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to Alexandria T. Phan, MD, director of GI Medical Oncology at Houston Methodist in Texas, who reported the subgroup results at the 2015 Gastrointestinal Cancers Symposium.1
On December 16, 2014, the FDA approved lanreotide to improve progression-free survival in patients with unresectable, well- or moderately differentiated, locally advanced or metastatic GEP-NETs. It is the first and only somatostatin analogue to gain approval in this setting, Phan noted.
In the CLARINET trial, treatment with lanreotide demonstrated significant prolongation of progression-free survival compared with placebo (HR = 0.47; 95% CI 0.30-0.73;P<.001).2,3The median PFS in the lanreotide arm had not been reached at the time of that analysis and was 16.6 months in the placebo arm.3
The results establish the antiproliferative effects of lanreotide, according to Caplin et al.2The somatostatin analogue octreotide is FDA-approved for symptomatic treatment of patients with functional NETs, based on data from the PROMID trial, but is not approved as an antiproliferative agent.
“The optimal frontline therapy has not been defined by existing prospective studies,” Phan said. In the conference abstract, Phan and colleagues indicated that the subgroup results support “a positive risk-benefit profile” for lanreotide as a first-line therapy for pNETs.
CLARINET was a phase III multicenter, randomized, double-blind, placebo-controlled 96-week randomized trial in which 204 patients received lanreotide 120 mg or placebo every 4 weeks, administered by deep subcutaneous injection. Patients had GEP-NETs, which includes midgut, hindgut, and pancreatic tumors.
The pNET planned subgroup analysis included 91 patients with nonfunctioning grade 1 or 2 tumors, representing about half of the broader CLARINET population. In this subgroup, 37% had hepatic tumor loads >25%, 95% had stable disease at baseline, 38% had undergone surgery, and 77% had received no previous medical treatment.
The median progression-free survival was not reached in pNET patients treated with lanreotide depot, but was 12.1 months in the placebo arm (95% CI, 9.4-18.3). This yielded a hazard ratio for progressive disease or death of 0.58 (95% CI, 0.32-1.04), Phan reported, noting that this indicated a favorable trend for lanreotide.
There were 18 events in the lanreotide arm, compared with 31 events in the placebo arm. In the lanreotide arm, 16 patients completed treatment without events, compared with nine in the placebo arm, she noted.
“The lanreotide treatment arm had more patients with disease control,” she emphasized.
Although mean exposure time was longer among patients who received lanreotide62 weeks versus 56 weeks for the placebo arm—the incidence of adverse events (AEs), defined as any events plus the most common events, was similar across the treatment arms, Phan reported.
AEs were reported by 88% of patients in each arm; diarrhea was the most commonly reported AE, reported by 43% in the lanreotide arm compared with 37% in the placebo group.
Serious AEs were reported by 29% of participants in the lanreotide arm, compared with 43% among those in the placebo arm. In all, only three patients reported treatment-related serious AEs, including two with lanreotide and one with placebo.
“The subgroup analysis raised no new safety concerns,” Phan said. “The positive risk-benefit profile for lanreotide depot in pNETs is consistent with the overall findings in CLARINET.”
George A. Fisher Jr, MD, PhD, professor of Medicine (Oncology) at Stanford University Medical Center and director of the Oncology Clinic, who moderated the session where CLARINET was presented, commented in an interview that he views the two somatostatin analogues as “interchangeable,” until further data might reveal differences.
Despite the progression-free survival improvement shown with lanreotide in CLARINET, he maintained that many asymptomatic patients should be observed, not treated right away. “There is nothing you lose by watching small-volume disease,” he said.
“I admit, a lot of this requires clinical judgment and experience, but if you are worried about a 10% tumor progressionbecause that might trigger jaundice, liver failure, symptoms—you could start on a somatostatin analogue right away,” said Fisher. “But in other patients you could wait, and do frequent monitoring. Patients’ tumors grow at different rates.”