FDA News

FDA approves Lutathera for gastroenteropancreatic neuroendocrine tumors

Jonathan Strosberg
Jonathan Strosberg

The FDA approved lutetium Lu 177 dotatate for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, including foregut, midgut and hindgut tumors.

Lutetium Lu 177 dotatate (Lutathera, Advanced Accelerator Applications) — a somatostatin analog peptide designed to target tumors with radiolabeled molecules that bind to specific receptors expressed by the tumor — is the first radiopharmaceutical approved for the treatment of gastroenteropancreatic neuroendocrine tumors.

“There are very few effective treatment options for patients with inoperable, advanced [gastroenteropancreatic neuroendocrine tumors] who are progressive on somatostatin analogues,” Jonathan Strosberg, MD, associate professor and section head of the neuroendocrine tumor program at Moffitt Cancer Center, said in a manufacturer-issued press release. “As a medical oncologist seeing more than 500 patients with [neuroendocrine tumors] each year, I am grateful to have another tool in my arsenal.

The FDA based this approval on results from the phase 3 NETTER-1 trial — which included 229 patients with inoperable midgut neuroendocrine tumors progressing under standard-dose octreotide long-acting repeatable (LAR; Sandostatin, Novartis) treatment and overexpressing somatostatin receptors — as well as a subset of data from an international, single-arm, open-label trial conducted in the Netherlands of 1,214 patients with somatostatin receptor-positive tumors.

In NETTER-1, researchers randomly assigned patients to lutetium Lu 177 dotatate plus octreotide LAR 30 mg every 4 weeks or 60 mg octreotide LAR alone every 4 weeks.

As HemOnc Today previously reported, lutetium Lu 177 dotatate conferred a 79% reduction in risk for disease progression or death (HR = 0.21; 95% CI, 0.13-0.32) compared with octreotide LAR. Median PFS was not reached in the lutetium Lu 177 dotatate arm compared with 8.5 months in the octreotide LAR arm.

Interim OS analysis showed a 48% risk reduction in the lutetium Lu 177 dotatate arm (HR = 0.52; 95% CI, 0.32-0.84).

Overall response rate was 13% for lutetium Lu 177 dotatate compared with 4% for octreotide LAR.

In the single-arm trial — which originally enrolled patients as part of an expanded access program — complete or partial tumor shrinkage occurred among 16% of patients from a subset of 360 patients with gastroenteropancreatic neuroendocrine tumors who the FDA evaluated for response.

“The approval of Lutathera marks an important achievement and innovation for the [neuroendocrine tumors] community,” Susanne Schaffert, PhD, chairperson and president of Advanced Accelerator Applications, said in the release. “As the first [peptide receptor radionuclide therapy] ever approved in the U.S., Lutathera is introducing a major advancement in the treatment paradigm for these patients that we hope will improve many lives. We believe nuclear medicine has the potential to offer many benefits to cancer patients and will use this approval as a foundation for the development of additional targeted cancer treatments utilizing radiolabeled ligands.”

Richard Pazdur, MD
Richard Pazdur

The most common grade 3 or grade 4 adverse reactions observed with lutetium Lu 177 dotatate in NETTER-1 included lymphopenia (44%), increased gamma-glutamyl transferase (20%), vomiting (7%), nausea and elevated aspartate aminotransferase (5% each), and increased alanine aminotransferase, hyperglycemia and hypokalemia (4% each).

“[Gastroenteropancreatic neuroendocrine tumors] are a rare group of cancers with limited treatment options after initial therapy fails to keep the cancer from growing,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “This approval provides another treatment choice for patients with these rare cancers. It also demonstrates how the FDA may consider data from therapies that are used in an expanded access program to support approval for a new treatment.”

Jonathan Strosberg
Jonathan Strosberg

The FDA approved lutetium Lu 177 dotatate for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, including foregut, midgut and hindgut tumors.

Lutetium Lu 177 dotatate (Lutathera, Advanced Accelerator Applications) — a somatostatin analog peptide designed to target tumors with radiolabeled molecules that bind to specific receptors expressed by the tumor — is the first radiopharmaceutical approved for the treatment of gastroenteropancreatic neuroendocrine tumors.

“There are very few effective treatment options for patients with inoperable, advanced [gastroenteropancreatic neuroendocrine tumors] who are progressive on somatostatin analogues,” Jonathan Strosberg, MD, associate professor and section head of the neuroendocrine tumor program at Moffitt Cancer Center, said in a manufacturer-issued press release. “As a medical oncologist seeing more than 500 patients with [neuroendocrine tumors] each year, I am grateful to have another tool in my arsenal.

The FDA based this approval on results from the phase 3 NETTER-1 trial — which included 229 patients with inoperable midgut neuroendocrine tumors progressing under standard-dose octreotide long-acting repeatable (LAR; Sandostatin, Novartis) treatment and overexpressing somatostatin receptors — as well as a subset of data from an international, single-arm, open-label trial conducted in the Netherlands of 1,214 patients with somatostatin receptor-positive tumors.

In NETTER-1, researchers randomly assigned patients to lutetium Lu 177 dotatate plus octreotide LAR 30 mg every 4 weeks or 60 mg octreotide LAR alone every 4 weeks.

As HemOnc Today previously reported, lutetium Lu 177 dotatate conferred a 79% reduction in risk for disease progression or death (HR = 0.21; 95% CI, 0.13-0.32) compared with octreotide LAR. Median PFS was not reached in the lutetium Lu 177 dotatate arm compared with 8.5 months in the octreotide LAR arm.

Interim OS analysis showed a 48% risk reduction in the lutetium Lu 177 dotatate arm (HR = 0.52; 95% CI, 0.32-0.84).

Overall response rate was 13% for lutetium Lu 177 dotatate compared with 4% for octreotide LAR.

In the single-arm trial — which originally enrolled patients as part of an expanded access program — complete or partial tumor shrinkage occurred among 16% of patients from a subset of 360 patients with gastroenteropancreatic neuroendocrine tumors who the FDA evaluated for response.

“The approval of Lutathera marks an important achievement and innovation for the [neuroendocrine tumors] community,” Susanne Schaffert, PhD, chairperson and president of Advanced Accelerator Applications, said in the release. “As the first [peptide receptor radionuclide therapy] ever approved in the U.S., Lutathera is introducing a major advancement in the treatment paradigm for these patients that we hope will improve many lives. We believe nuclear medicine has the potential to offer many benefits to cancer patients and will use this approval as a foundation for the development of additional targeted cancer treatments utilizing radiolabeled ligands.”

Richard Pazdur, MD
Richard Pazdur

The most common grade 3 or grade 4 adverse reactions observed with lutetium Lu 177 dotatate in NETTER-1 included lymphopenia (44%), increased gamma-glutamyl transferase (20%), vomiting (7%), nausea and elevated aspartate aminotransferase (5% each), and increased alanine aminotransferase, hyperglycemia and hypokalemia (4% each).

“[Gastroenteropancreatic neuroendocrine tumors] are a rare group of cancers with limited treatment options after initial therapy fails to keep the cancer from growing,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “This approval provides another treatment choice for patients with these rare cancers. It also demonstrates how the FDA may consider data from therapies that are used in an expanded access program to support approval for a new treatment.”