麻豆传媒

PHILADELPHIA -- Treatment with 177Lu-Dotatate (Lutathera) offered a quality of life (QoL) benefit to patients with midgut neuroendocrine tumors, researchers said here.

Compared with patients on a high-dose of somatostatin analog octreotide LAR, patients with midgut neuroendocrine tumors (NETs) given 177Lu reported a significantly longer time to QoL deterioration across several domains, reported Jonathan Strosberg, MD, of Moffitt Cancer Center in Tampa, Florida, and colleagues, in a presentation at the North American Neuroendocrine Tumor Society annual symposium.

QoL scores were higher with 177Lu across the following domains:

• Global health status: hazard ratio 0.406, 22.7-month difference (P=0.0006)
• Physical functioning: HR 0.518, 13.7 months difference (P=0.0147)
• Role functioning: HR 0.580 (P=0.0298)
• Fatigue: HR 0.621 (P=0.0297)
• Pain: HR 0.566 (P=0.0247)
• Diarrhea: HR 0.473 (P=0.0107)
• Disease related worries: HR 0.572 (P=0.0176)
• Body image: HR 0.425 (P=0.0058)

"We were pleasantly surprised by the magnitude of positive impact of treatment with 177-Lutetium-Dotatate on quality of life," Strosberg told 麻豆传媒. "For example, time to deterioration in global health improved from a median of roughly 6 months with high dose octreotide, to nearly 29 months with 177-Lu-Dotatate."

The primary endpoint of the phase III, international was comparison of progression-free survival (PFS) between treatment groups, while was one of the trial's secondary endpoints.

"Health related quality of life [HRQoL] is increasingly becoming a critical secondary endpoint in randomized clinical trials," Strosberg said. "It is important to demonstrate that treatments not only impact radiographic progression, but also provide a meaningful benefit to patient well-being. For that reason, analyzing HRQoL on the NETTER 1 trial ... was a high priority."

The trial included 231 participants, ages ≥18, with somatostatin receptor positive midgut NETs who were followed-up for 5 years. After randomization, 117 participants were assigned to receive 4 doses of 7.4 GBq of 177Lu plus somatostatin analogues (SSAs) for symptom control. The 114 control participants received 60 mg of octreotide LAR every 4 weeks.

All participants had locally advanced or metastatic histologically proven, well-differentiated midgut NETs that were inoperable. All had progressive disease, defined by RECIST criteria, with a high Ki-67 protein index of 20% or greater and a Karnofsky performance score of ≥60. Participants were also on a fixed, uninterrupted dose of 20-30 mg of octreotide LAR, every 3-4 weeks.

The participants were administered questionnaires every 12 weeks after baseline until disease progression. Scores were then converted to a 100-point scale to assess individual changes in time to deterioration from baseline, measured in months.

Other QoL domains, including flushing and sweats, did not show a significant improvement in the 177Lu group due to an improvement in both study arms. However, there was a slightly better, yet insignificant favor towards 177Lu treatment. No domains reported a significantly longer time to quality of life deterioration for the octreotide LAR group.

Treatment-related adverse events were higher in the 177Lu group, with 86% reported any adverse event, compared with 31% of octreotide LAR treatment. Serious adverse events related to treatment were reported in 9% of 177Lu recipients versus 1% of controls. No participants on octreotide LAR treatment withdrew from the study due to treatment-related adverse events, while 5% of 177Lu participants did.

"The NETTER 1 study was the first randomized prospective trial of a radiolabeled somatostatin analog. We are also looking forward to the , which will randomized patients with nonfunctioning gastroenteropancreatic NETs to 177-Lutetium-Dotatoc versus everolimus," Strosberg noted.

developer Advanced Accelerator Applications announced receipt of a Complete Response Letter regarding a FDA New Drug Application in December 2016.

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