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Advanced metastatic midgut neuroendocrine tumors: New drug in development shows improved progression-free survival for patients

Date:
January 12, 2017
Source:
H. Lee Moffitt Cancer Center & Research Institute
Summary:
A new therapy in development for the treatment of midgut neuroendocrine tumors, a rare type of cancer that occurs in the small intestine and colon, shows improved progression-free survival and response rates for patients with advanced disease.
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A new therapy in development for the treatment of midgut neuroendocrine tumors, a rare type of cancer that occurs in the small intestine and colon, shows improved progression-free survival and response rates for patients with advanced disease. Results of the international phase 3 clinical trial of lutetium-177 (177Lu)-Dotatate compared to high-dose octreotide LAR were published in the Jan. 12 issue of 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 analog 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 analog therapy, there are currently not many other treatment options.

Moffitt is one of 41 cancer centers worldwide to investigate a novel therapy, 177Lu-Dotatate. The drug consists of a radioactive molecule attached to a somatostatin analog, 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 analog, 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 progression-free survival rate was 65.2 percent in the 177Lu-Dotatate group and 10.8 percent in the control group. 177Lu-Dotatate-treated patients had a 79 percent 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 percent versus 3 percent).

"This is notable given that response rates above 5 percent have not been observed in large randomized clinical trials of other systemic therapies in this patient population," said Dr. Strosberg. "The clinically meaningful and statistically significant improvement in progression-free survival and response rates achieved with treatment of 177Lu-Dotatate when compared to high dose octreotide supports its use in the treatment of neuroendocrine tumor patients. As a clinician treating many patients with this condition, these results bring hope for our ability to improve lives."

The trial data showed that 177Lu-Dotatate-treated patients experienced more adverse events than control patients (86 percent versus 31 percent), but the toxicities were manageable and reversible. The most common adverse events with 177Lu-Dotatate were nausea and vomiting, but 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 currently being reviewed by the U.S. Food and Drug Administration.


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Materials provided by H. Lee Moffitt Cancer Center & Research Institute. Note: Content may be edited for style and length.


Journal Reference:

  1. Jonathan Strosberg, Ghassan El-Haddad, Edward Wolin, Andrew Hendifar, James Yao, Beth Chasen, Erik Mittra, Pamela L. Kunz, Matthew H. Kulke, Heather Jacene, David Bushnell, Thomas M. O’Dorisio, Richard P. Baum, Harshad R. Kulkarni, Martyn Caplin, Rachida Lebtahi, Timothy Hobday, Ebrahim Delpassand, Eric Van Cutsem, Al Benson, Rajaventhan Srirajaskanthan, Marianne Pavel, Jaime Mora, Jordan Berlin, Enrique Grande, Nicholas Reed, Ettore Seregni, Kjell Öberg, Maribel Lopera Sierra, Paola Santoro, Thomas Thevenet, Jack L. Erion, Philippe Ruszniewski, Dik Kwekkeboom, Eric Krenning. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. New England Journal of Medicine, 2017; 376 (2): 125 DOI: 10.1056/NEJMoa1607427

Cite This Page:

H. Lee Moffitt Cancer Center & Research Institute. "Advanced metastatic midgut neuroendocrine tumors: New drug in development shows improved progression-free survival for patients." ScienceDaily. ScienceDaily, 12 January 2017. <www.sciencedaily.com/releases/2017/01/170112110842.htm>.
H. Lee Moffitt Cancer Center & Research Institute. (2017, January 12). Advanced metastatic midgut neuroendocrine tumors: New drug in development shows improved progression-free survival for patients. ScienceDaily. Retrieved May 26, 2017 from www.sciencedaily.com/releases/2017/01/170112110842.htm
H. Lee Moffitt Cancer Center & Research Institute. "Advanced metastatic midgut neuroendocrine tumors: New drug in development shows improved progression-free survival for patients." ScienceDaily. www.sciencedaily.com/releases/2017/01/170112110842.htm (accessed May 26, 2017).

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