A new therapy in development for the treatment of midgut neuroendocrine tumors, a rare cancer that occurs in the small intestine and colon, shows improved progression-free survival (PFS) and response rates for patients with advanced disease. Results of the international phase 3 clinical trial of lutetium-177 (177Lu-Dotatate compared with high-dose octreotide long-acting repeatable were published in the New England Journal of Medicine.
“Patients diagnosed with midgut neuroendocrine tumors often have advanced disease that has spread to other sites. Treatment options are limited. 177Lu-Dotatate is an effective option to delay tumor progression for patients with this disease,” says Jonathan R. Strosberg, head of the Neuroendocrine Tumor Program at Moffitt Cancer Center. “There is also preliminary evidence of survival benefit that requires confirmation on final survival analysis, expected in several years.”
Standard treatment for midgut neuroendocrine tumors is hormonal therapy using a somatostatin analogue that blocks the growth of tumor cells and reduces the production of hormones that cause symptoms, such as flushing and diarrhea. If a patient’s tumors progress on somatostatin analogue therapy, there are few other treatment options.
Moffitt is one of 41 cancer centers worldwide to investigate the novel therapy 177Lu-Dotatate. The drug consists of a radioactive molecule attached to a somatostatin analogue, allowing for radiation to be directly targeted to somatostatin-receptor–expressing tumors. Patients with metastatic or locally advanced midgut neuroendocrine tumors that had disease progression during prior treatment with octreotide, a somatostatin analogue, were enrolled in the trial.
Trial results showed that patients who were treated with 177Lu-Dotatate and octreotide had better outcomes than patients who were treated with high-dose octreotide alone. The 20-month PFS rate was 65.2% in the 177Lu-Dotatate group and 10.8% in the control group. 177Lu-Dotatate-treated patients had a 79% lower risk of disease progression or death than the control patients over the follow-up period. Additionally, more patients treated with 177Lu-Dotatate achieved a radiographic response than patients in the control group (18% versus 3%).
“This is notable given that response rates above 5% have not been observed in large randomized clinical trials of other systemic therapies in this patient population,” said Dr. Strosberg.
The trial data showed that 177Lu-Dotatate-treated patients experienced more adverse events than control patients (86% versus 31%), but the toxicities were manageable and reversible. The most common adverse events with 177Lu-Dotatate were nausea and vomiting; this was attributed to amino acid infusions that were given to the patients to relieve potential kidney toxicity. Toxicities that occurred more in the 177Lu-Dotatate-treated patients included thrombocytopenia, anemia, lymphopenia, and leukopenia.
The clinical trial was supported by Advanced Accelerator Applications, developer of 177Lu-Dotatate. A new drug application for 177Lu-Dotatate is being reviewed by the FDA.
Source: Moffitt Cancer Center; January 12, 2017.