Radiolabeled somatostatin analogue linked with improved survival in neuroendocrine tumors

1. ¹⁷⁷Lu-Dotatate, a radiolabeled somatostatin analogue, was associated with increased progression-free survival and decreased overall mortality compared to standard therapy in the treatment of metastatic neuroendocrine tumors of the midgut.

2. ¹⁷⁷Lu-Dotatate therapy was linked with an increased risk of hematologic side effects as well as nausea and vomiting compared to standard therapy with best supportive care and long-acting octreotide.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Associated with a poor 5-year survival, neuroendocrine tumors of the midgut (including jejunoileum and the proximal colon) commonly metastasize and are associated with carcinoid syndrome. Beyond the use of a somatostatin analogue, there are few to no second-line therapies for this condition, but research into targeted somatostatin therapies has shown promise. In NETTER-1, an open-label, phase 3 randomized controlled trial, the authors probed the efficacy and safety of a radiolabeled somatostatin analogue, ¹⁷⁷Lu-Dotatate, in patients with advanced, progressive midgut neuroendocrine tumors. The trial involved 229 patients. Compared to best supportive care including octreotide long-acting repeatable, a combination of ¹⁷⁷Lu-Dotatate and octreotide infusions was associated with significantly higher rates of progression-free survival at month 20, a higher objective response rate, and a lower number of deaths. At the same time, the ¹⁷⁷Lu-Dotatate experienced a higher number of adverse events, including thrombocytopenia, lymphopenia, and nausea and vomiting, though they did not have appreciably worse renal outcomes.

Click to read the study, published today in NEJM

Relevant Reading: Treatment of the Malignant Carcinoid Syndrome

In-Depth [randomized controlled trial]: This trial spanned 41 centers in 8 countries, and involved 229 patients with well-differentiated, metastatic neuroendocrine tumors of the midgut. Participants were randomized to receive either long-acting octreotide and best supportive care versus a group including these interventions as well as ¹⁷⁷Lu-Dotatate therapy, administered concomitantly with a renal-protective agent. The estimated rate of progression-free survival at the pre-specified data cut-off (month 20) was 65.2% (95%CI 50 to 76.8) in the ¹⁷⁷Lu-Dotatate group and 10.8% (95%CI 3.5 to 23) in the control group; the hazard ratio for disease progression or death with ¹⁷⁷Lu-Dotatate therapy versus control was 0.21 (95%CI 0.13 to 0.33; p < 0.001), a finding that held across prespecified subgroups and prognostic factors. The estimated risk of death in the ¹⁷⁷Lu-Dotatate group was 60% lower than the control group (HR 0.40, p = 0.004). Grade 3 or 4 thrombocytopenia and lymphopenia, as well as nausea, vomiting, and asthenia were significantly more likely to occur in the ¹⁷⁷Lu-Dotatate group compared to control, though there was no evidence of renal toxic effects in the ¹⁷⁷Lu-Dotatate group.

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