The results of three recent, practice-changing Phase III clinical trials were presented for the first time in North America at the NANETS symposium which included: (1) TELESTAR (randomized Phase III trial of telotristat vs. placebo in patients with carcinoid syndrome), (2) NETTER-1 (randomized Phase III trial of 177-Lu-DOTATATE vs. high dose octreotide in patients with progressive midgut NETs), and (3) RADIANT-4 (randomized Phase III trial of everolimus vs. placebo in advanced non-functional GI and lung NETs). NANETS will continue to keep you informed on the progress of the regulatory submissions for all three of these treatments.

Following are brief descriptions of the data:

Trial 1

In the Phase III TELESTAR study, telotristat etiprate, an oral inhibitor of tryptophan hydroxylase – the rate limiting step in serotonin synthesis — decreased mean daily bowel movements by 35% among participants (n=135) who received 500 mg of the drug three times a day and 29% among those who took 250 mg three times a day, compared with 17% for individuals who received a placebo. The results, measured from baseline to 12 weeks, were statistically significant (p <.001). Urinary 5-HIAA levels were significantly reduced in patients receiving telotristat compared to placebo, suggesting effective inhibition of serotonin production. Read more at OncLive.

Trial 2

The Phase III NETTER-1 trial compared the efficacy of 177-Lu-Dotatate (Lutathera) (n=116) with octreotide 60 mg (Sandostatin LAR) (n=113) in patients with advanced progressive disease. Results showed that the median progression-free survival (PFS), the trial's primary endpoint, improved by nearly 80% (HR 0.21, 95% CI 0.13-0.34). The median PFS with high-dose octreotide was 8.4 months and was not yet reached in the 177-Lu-Dotatate arm at a median follow-up of 18 months. Read more at OncLive.

Trial 3

The Phase III RADIANT-4 trial was a study of advanced, progressive, nonfunctional lung/GI NETs. In the study, 302 patients with progressive, well-differentiated, nonfunctional lung/GI NETs were randomized 2:1 to receive best supportive care plus either everolimus at 10 mg per day (n = 205) or placebo (n = 97). Tumors were located in the GI tract (n = 175), lung (n = 90), or were of unknown origin (n = 36). The primary endpoint was progression free survival (PFS); the progression free survival was 11 months on the everolimus arm compared to 3.9 months in the placebo arm (HR 0.48, 95% CI, 0.35-0.67). Read more at OncLive.