Radioligand Therapy Improves PFS and Responses in SSTR+ Grade 2/3 GEP-NETs


Results from the phase 3 NETTER-2 study will be presented at an upcoming medical conference and shared with drug regulators.

Pamela Kunz, MD

Pamela Kunz, MD

The use of lutetium 177Lu dotatate (Lutathera) and high-dose long-acting octreotide as frontline treatment for patients with newly diagnosed somatostatin receptor (SSTR)-positive, grade 2 and 3, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) led to significant improvements in progression-free survival (PFS) compared with high-dose long-acting octreotide alone.1

"In 2018, 177Lu dotatate was FDA approved for metastatic SSTR-positive GEPNETs on the basis of the NETTER-1 clinical trial. In that trial, patients received 177Lu dotatate after progression on SSAs, therefore, 177 Lu dotatate is generally used in the second-line setting after progression on SSA or other therapies, Pamela Kunz, MD told Targeted Oncology.TM "The NETTER-2 clinical trial examined 2 new questions. Is 177Lu dotatate effective in the 1st line setting? Secondly, is 177Lu dotatate effective in patients with higher Ki67 [Ki 67 10%-55%]. The information suggests 'yes' – though we do not have data on specific subsets," she said.

Findings come from the phase 3 NETTER-2 clinical trial (NCT03972488), which also showed that the lutetium 177Lu dotatate reached the secondary end point of objective response rate (ORR) and showed no new or unexpected safety signals. Results from the study will be presented at an upcoming medical conference and shared with drug regulators.

Dna. | Image Credit: © -

DNA | Image Credit: © -

“These positive results for [177Lu dotatate] are quite remarkable and they represent the potential for radioligand therapy to make a meaningful impact for newly diagnosed patients living with advanced GEP-NETs,” said Jeff Legos, executive vice president, global head of oncology development at Novartis, in a press release. “Exploring the use of radioligand therapies in earlier lines of treatment for patients with cancer is part of our larger, collaborative effort to precisely deliver novel treatment modalities directly to the cancer cells to improve patient outcomes.”

NETTER-2 is a multi-center, randomized, open-label study. Patients in the radioligand therapy arm of the study are treated with either 177Lu dotatate 7.4 GBq/200 mCi x 4, given about every 8 weeks with long-acting octreotide 30 mg every 8 weeks, and optional post-progression re-treatment with 177Lu dotatate for an additional 4 to 6 cycles. In the comparator arm, patients will receive high-dose long-acting octreotide at 60 mg every 4 weeks, with optional post-progression cross-over to 177Lu dotatate 7.4 GBq/200 mCi x 4 cycles plus octreotide long-acting at 30 mg every 8 weeks.2

In addition to PFS and ORR, the study is investigating the secondary end points of the time to decline in global health status, disease control rate, duration of response, rate of adverse events, rate of laboratory toxicities, and time to death.

Recruitment of patients in the NETTER-2 study has been completed. The population enrolled were children and adults aged 15 years or older who had a presence of metastasized or locally advanced, inoperable, histologically proven, well differentiated grade 2 or grade 3 GEP-NETs. At baseline, patients were required to have a Ki67 index ≥10 and ≤ 55%, somatostatin receptors expression in all target lesions documented by CT/MRI scans, normal liver uptake on target lesions, a Karnofsky performance score ≥ 60, and at least 1 measurable lesion.

"This would represent a new indication for first-line treatment of GEP-NETS. In addition, this would represent the first theranostic agent FDA approved for use in the 1st line setting," said Kunz, associate professor of Internal Medicine (Medical Oncology); director, Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center; chief, GI Medical Oncology; vice chief, Diversity, Equity, and Inclusion, Medical Oncology.


1. Novartis radioligand therapy Lutathera® demonstrated statistically significant and clinically meaningful progression-free survival in first line advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). News release. September 25, 2023. Accessed September 25, 2023.

2. Study to evaluate the efficacy and safety of Lutathera in patients with grade 2 and grade 3 advanced GEP-NET (NETTER-2). Updated July 27, 2023. Accessed September 25, 2023.

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