Novel radiopharmaceutical delivers "impressive" results in midgut NET

Last Updated: 2016-01-21

By Megan Brooks

NEW YORK (Reuters Health) - Lutetium-labeled octreotide (177Lu-DOTATATE, Lutathera) has shown significant promise in patients with previously treated advanced midgut neuroendocrine tumors (NETs) in the first randomized controlled trial of the treatment.

In the phase 3 NETTER-1 trial, treating patients with this radiolabeled somatostatin analogue significantly lowered their risk of disease progression or death, compared with treatment with standard octreotide long-acting release (LAR).

Dr. Jonathan R. Strosberg, a medical oncologist at the Moffitt Cancer Center in Tampa, Florida, presented the findings January 19 during a press briefing ahead of the 2016 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, which gets underway today in San Francisco.

"While there have been few available systemic treatment options for patients progressing on first-line somatostatin analogues, Lutathera has a major therapeutic benefit for this patient population," he told the briefing.

Most patients with midgut NETs receive first-line treatment with a somatostatin analog such as octreotide or lanreotide. When that fails, second-line options are limited, he explained.

The NETTER-1 trial enrolled 230 patients with inoperable midgut NET with disease progression following first-line somatostatin analog therapy. Patients were randomly allocated to four courses of 177Lu-DOTATATE (7.4 GBq every eight weeks) or high-dose octreotide LAR (60 mg every four weeks). There were 115 patients in each group.

At the time of data analysis, far fewer patients in the 177Lu-DOTATATE group than the octreotide LAR group had experienced disease progression (23 vs. 67 patients).

Median progression-free survival (the primary endpoint) was not yet reached in the 177Lu-DOTATATE arm and was 8.4 months in the octreotide LAR arm (p<0.0001), translating into a 79% reduction in risk for progression or death with 177Lu-DOTATATE, Dr. Strosberg reported.

"With roughly a year and a half duration of follow-up thus far, we can see from the Kaplan-Meier curve that the expected median (progression-free survival) is likely to be longer than three years on the experimental arm," he said.

In addition, objective response rates were significantly higher in the 177Lu-DOTATATE arm than the octreotide LAR arm (18% vs. 3%; p=0.0008).

Preliminary data also suggest an improvement in overall survival with 177Lu-DOTATATE, with 13 deaths in that arm versus 22 in the octreotide arm (p<0.019 at interim analysis). Dr. Strosberg cautioned, however, that this is the first interim look at overall survival and longer follow-up is needed to determine any definitive impact on long-term survival.

In terms of toxicity, 177Lu-DOTATATE was "quite well tolerated," he noted, "and this refers to all grades and grade 3-4. Grade 3-4 were all in the single digits."

There were no marked between-group differences in numbers of adverse events, including serious side effects. Octreotide often causes gas and bloating and can lead to gallstone development with long-term use, while 177Lu-DOTATATE may transiently lower blood cell counts, an ASCO news release notes.

"Our results indicate that Lutathera appears to be a safe and effective treatment option. On average, tumors responded to the drug for several years before they began growing again," Dr. Strosberg said in the release. "The new therapy is also more convenient - it requires only four treatments, as opposed to medications that patients have to take daily over long periods of time."

Commenting on the results, ASCO spokesperson and briefing moderator Dr. Smitha Krishnamurthi said, "Lutetium DOTATATE showed impressive ability to slow the growth of midgut neuroendocrine tumors that progressed on somatostatin analogue therapy. Also notable was that Lutetium DOTATATE resulted in a response rate of 18% in these tumors which are typically unresponsive to systemic therapy."

Lutathera is being developed by Advanced Accelerator Applications, which funded the study. Dr. Strosberg has no relevant disclosures. One author has received research funding from Advanced Accelerator Applications.