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VIENNA – After posting unprecedented results in the phase III NETTER-1 trial, the experimental radiopeptide therapy 177Lu-Dotatate looks poised to become a new treatment option for patients with midgut neuroendocrine tumors that progress on somatostatin analogues.
Median progression-free survival was not reached in patients receiving 177Lu-Dotatate (Lutathera) plus the somatostatin octreotide LAR (Sandostatin), the current standard of care, and was 8.4 months in those given a double dose of octreotide LAR.
This resulted in a hazard ratio of 0.209 (P less than .0001) or almost an 80% reduction in the risk for disease progression or death, Dr. Philippe Ruszniewski of Beaujon Hospital in Clichy, France, said at the European Society for Medical Oncology Congress.
The experimental therapy also was superior to octreotide LAR in terms of objective response rate (19% vs. 3%; P less than .0004). This included one complete response and 18 partial responses to 177Lu-Dotatate vs. 3 partial responses to octreotide LAR alone.
Although few treatment options were up to now available for this rare cancer, “Lu-Dotatate appears as a major advance in these patients,” he said.
Invited discussant Dr. Enrique Grande of Ram<scaps>ó</scaps>n y Cajal University Hospital in Madrid, commented, “This is the most impressive cohort in terms of progression-free survival that we have seen in the neuroendocrine tumors … especially since the comparator arm is a really active one that we are doing in routine practice.”
177Lu-Dotatate belongs to a drug category called peptide receptor radionuclide therapy and is composed of a lutetium radionuclide chelated to a peptide. The 177Lutetium-labeled somatostatin analogue peptide targets somatostatin receptors, which are overexpressed in about 80% of neuroendocrine tumors (NETs).
177Lu-Dotatate has received orphan drug status from the Food and Drug Administration and the European Medicines Agency and in April 2015 also was granted fast-track designation by the FDA.
NETTER-1 enrolled 230 patients with metastatic or locally advanced, inoperable midgut NETs, functioning or not, and evenly randomized them to four doses of 7.4 GBq 177Lu-Dotatate intravenously over 8 weeks plus octreotide LAR 30 mg or to octreotide LAR 60 mg every 28 days given as a deep intragluteal injection. The ileum was the primary tumor site in three-fourths of patients and the liver the site of metastasis in about 83%.
Three-fourths of patients received all four doses of 177Lu-Dotatate and no dose-modifying toxicity was observed in 95% of all 111 treated patients, Dr. Ruszniewski said.
An interim analysis suggested increased overall survival (13 deaths vs. 22 deaths; P less than .018), but the data are immature and need to be confirmed by final analysis, he said.
Treatment-related adverse events of any grade were reported in 86% of patients given 177Lu-Dotatate and 31% on octreotide LAR 60 mg.
Treatment-related serious events occurred in 10 patients in the 177Lu-Dotatate arm vs. 1 in the octreotide arm, with withdrawals because of treatment-related adverse events in 5 vs. 0 patients, respectively.
Serious adverse events related to 177Lu-Dotatate included, but were not limited to, lymphocytopenia in seven patients, thrombocytopenia in three, acute kidney injury in two, and one case each of renal failure and portal hypertension.
When asked in a press briefing whether 177Lu-Dotatate could induce long-term DNA damage after hitting its target, Dr. Ruszniewski said a substudy in 20 unrelated patients will provide pharmacokinetic data on the fate of the radionuclide.
“What we know from phase I and II is that this is probably possible, but rare,” he said. “The two organs that should be carefully watched are the bone marrow and the kidneys.”
To reduce kidney damage, amino acids are infused at the same time as the radionuclide. Myelodysplastic syndrome might occur in 3% to 4% of patients, he added.
The investigators called for additional studies of 177Lu-Dotatate in other types of NETs such as pancreatic and bronchial.
When it was noted that the approved radioactive agent, radium-223 dichloride (Xofigo) also has very good data in pancreatic cancer but is often used behind other drugs because it is a radiopharmaceutical, Dr. Ruszniewski dismissed the suggestion and said NETs are a completely different disease.
Discussant Dr. Grande, however, said that there are logistical considerations surrounding 177-Lu-Dotatate, such as how clinicians would request it, whether it will be widely available, and where it would be delivered.
No special room is needed to treat patients with 177-Lu-Dotatate, but patient urine does have to be controlled, Dr. Ruszniewski noted.
On Twitter @pwendl
VIENNA – After posting unprecedented results in the phase III NETTER-1 trial, the experimental radiopeptide therapy 177Lu-Dotatate looks poised to become a new treatment option for patients with midgut neuroendocrine tumors that progress on somatostatin analogues.
Median progression-free survival was not reached in patients receiving 177Lu-Dotatate (Lutathera) plus the somatostatin octreotide LAR (Sandostatin), the current standard of care, and was 8.4 months in those given a double dose of octreotide LAR.
This resulted in a hazard ratio of 0.209 (P less than .0001) or almost an 80% reduction in the risk for disease progression or death, Dr. Philippe Ruszniewski of Beaujon Hospital in Clichy, France, said at the European Society for Medical Oncology Congress.
The experimental therapy also was superior to octreotide LAR in terms of objective response rate (19% vs. 3%; P less than .0004). This included one complete response and 18 partial responses to 177Lu-Dotatate vs. 3 partial responses to octreotide LAR alone.
Although few treatment options were up to now available for this rare cancer, “Lu-Dotatate appears as a major advance in these patients,” he said.
Invited discussant Dr. Enrique Grande of Ram<scaps>ó</scaps>n y Cajal University Hospital in Madrid, commented, “This is the most impressive cohort in terms of progression-free survival that we have seen in the neuroendocrine tumors … especially since the comparator arm is a really active one that we are doing in routine practice.”
177Lu-Dotatate belongs to a drug category called peptide receptor radionuclide therapy and is composed of a lutetium radionuclide chelated to a peptide. The 177Lutetium-labeled somatostatin analogue peptide targets somatostatin receptors, which are overexpressed in about 80% of neuroendocrine tumors (NETs).
177Lu-Dotatate has received orphan drug status from the Food and Drug Administration and the European Medicines Agency and in April 2015 also was granted fast-track designation by the FDA.
NETTER-1 enrolled 230 patients with metastatic or locally advanced, inoperable midgut NETs, functioning or not, and evenly randomized them to four doses of 7.4 GBq 177Lu-Dotatate intravenously over 8 weeks plus octreotide LAR 30 mg or to octreotide LAR 60 mg every 28 days given as a deep intragluteal injection. The ileum was the primary tumor site in three-fourths of patients and the liver the site of metastasis in about 83%.
Three-fourths of patients received all four doses of 177Lu-Dotatate and no dose-modifying toxicity was observed in 95% of all 111 treated patients, Dr. Ruszniewski said.
An interim analysis suggested increased overall survival (13 deaths vs. 22 deaths; P less than .018), but the data are immature and need to be confirmed by final analysis, he said.
Treatment-related adverse events of any grade were reported in 86% of patients given 177Lu-Dotatate and 31% on octreotide LAR 60 mg.
Treatment-related serious events occurred in 10 patients in the 177Lu-Dotatate arm vs. 1 in the octreotide arm, with withdrawals because of treatment-related adverse events in 5 vs. 0 patients, respectively.
Serious adverse events related to 177Lu-Dotatate included, but were not limited to, lymphocytopenia in seven patients, thrombocytopenia in three, acute kidney injury in two, and one case each of renal failure and portal hypertension.
When asked in a press briefing whether 177Lu-Dotatate could induce long-term DNA damage after hitting its target, Dr. Ruszniewski said a substudy in 20 unrelated patients will provide pharmacokinetic data on the fate of the radionuclide.
“What we know from phase I and II is that this is probably possible, but rare,” he said. “The two organs that should be carefully watched are the bone marrow and the kidneys.”
To reduce kidney damage, amino acids are infused at the same time as the radionuclide. Myelodysplastic syndrome might occur in 3% to 4% of patients, he added.
The investigators called for additional studies of 177Lu-Dotatate in other types of NETs such as pancreatic and bronchial.
When it was noted that the approved radioactive agent, radium-223 dichloride (Xofigo) also has very good data in pancreatic cancer but is often used behind other drugs because it is a radiopharmaceutical, Dr. Ruszniewski dismissed the suggestion and said NETs are a completely different disease.
Discussant Dr. Grande, however, said that there are logistical considerations surrounding 177-Lu-Dotatate, such as how clinicians would request it, whether it will be widely available, and where it would be delivered.
No special room is needed to treat patients with 177-Lu-Dotatate, but patient urine does have to be controlled, Dr. Ruszniewski noted.
On Twitter @pwendl
VIENNA – After posting unprecedented results in the phase III NETTER-1 trial, the experimental radiopeptide therapy 177Lu-Dotatate looks poised to become a new treatment option for patients with midgut neuroendocrine tumors that progress on somatostatin analogues.
Median progression-free survival was not reached in patients receiving 177Lu-Dotatate (Lutathera) plus the somatostatin octreotide LAR (Sandostatin), the current standard of care, and was 8.4 months in those given a double dose of octreotide LAR.
This resulted in a hazard ratio of 0.209 (P less than .0001) or almost an 80% reduction in the risk for disease progression or death, Dr. Philippe Ruszniewski of Beaujon Hospital in Clichy, France, said at the European Society for Medical Oncology Congress.
The experimental therapy also was superior to octreotide LAR in terms of objective response rate (19% vs. 3%; P less than .0004). This included one complete response and 18 partial responses to 177Lu-Dotatate vs. 3 partial responses to octreotide LAR alone.
Although few treatment options were up to now available for this rare cancer, “Lu-Dotatate appears as a major advance in these patients,” he said.
Invited discussant Dr. Enrique Grande of Ram<scaps>ó</scaps>n y Cajal University Hospital in Madrid, commented, “This is the most impressive cohort in terms of progression-free survival that we have seen in the neuroendocrine tumors … especially since the comparator arm is a really active one that we are doing in routine practice.”
177Lu-Dotatate belongs to a drug category called peptide receptor radionuclide therapy and is composed of a lutetium radionuclide chelated to a peptide. The 177Lutetium-labeled somatostatin analogue peptide targets somatostatin receptors, which are overexpressed in about 80% of neuroendocrine tumors (NETs).
177Lu-Dotatate has received orphan drug status from the Food and Drug Administration and the European Medicines Agency and in April 2015 also was granted fast-track designation by the FDA.
NETTER-1 enrolled 230 patients with metastatic or locally advanced, inoperable midgut NETs, functioning or not, and evenly randomized them to four doses of 7.4 GBq 177Lu-Dotatate intravenously over 8 weeks plus octreotide LAR 30 mg or to octreotide LAR 60 mg every 28 days given as a deep intragluteal injection. The ileum was the primary tumor site in three-fourths of patients and the liver the site of metastasis in about 83%.
Three-fourths of patients received all four doses of 177Lu-Dotatate and no dose-modifying toxicity was observed in 95% of all 111 treated patients, Dr. Ruszniewski said.
An interim analysis suggested increased overall survival (13 deaths vs. 22 deaths; P less than .018), but the data are immature and need to be confirmed by final analysis, he said.
Treatment-related adverse events of any grade were reported in 86% of patients given 177Lu-Dotatate and 31% on octreotide LAR 60 mg.
Treatment-related serious events occurred in 10 patients in the 177Lu-Dotatate arm vs. 1 in the octreotide arm, with withdrawals because of treatment-related adverse events in 5 vs. 0 patients, respectively.
Serious adverse events related to 177Lu-Dotatate included, but were not limited to, lymphocytopenia in seven patients, thrombocytopenia in three, acute kidney injury in two, and one case each of renal failure and portal hypertension.
When asked in a press briefing whether 177Lu-Dotatate could induce long-term DNA damage after hitting its target, Dr. Ruszniewski said a substudy in 20 unrelated patients will provide pharmacokinetic data on the fate of the radionuclide.
“What we know from phase I and II is that this is probably possible, but rare,” he said. “The two organs that should be carefully watched are the bone marrow and the kidneys.”
To reduce kidney damage, amino acids are infused at the same time as the radionuclide. Myelodysplastic syndrome might occur in 3% to 4% of patients, he added.
The investigators called for additional studies of 177Lu-Dotatate in other types of NETs such as pancreatic and bronchial.
When it was noted that the approved radioactive agent, radium-223 dichloride (Xofigo) also has very good data in pancreatic cancer but is often used behind other drugs because it is a radiopharmaceutical, Dr. Ruszniewski dismissed the suggestion and said NETs are a completely different disease.
Discussant Dr. Grande, however, said that there are logistical considerations surrounding 177-Lu-Dotatate, such as how clinicians would request it, whether it will be widely available, and where it would be delivered.
No special room is needed to treat patients with 177-Lu-Dotatate, but patient urine does have to be controlled, Dr. Ruszniewski noted.
On Twitter @pwendl
AT EUROPEAN CANCER CONGRESS 2015
Key clinical point: 177Lu-Dotatate plus octreotide LAR was superior to a double-dose of octreotide LAR in terms of progression-free survival and overall response in progressive midgut neuroendocrine tumors.
Major finding: Median progression-free survival was not reached for 177Lu-Dotatate plus octreotide LAR; it was 8.4 months for high-dose octreotide LAR (hazard ratio, 0.2; P less than .001).
Data source: Phase III trial in 230 patients with progressive midgut NETs.
Disclosures: Advanced Accelerator Applications funded the study. Dr. Ruszniewski reported serving as an advisor to AAA and has received honoraria and research funding from AAA, Ipsen, and Novartis.
