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.
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.
©2017 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.