First-Line Lutetium Lu 177 Dotatate Plus Octreotide Improves PFS in Advanced Gastroenteropancreatic NETs

September 25, 2023

First-line treatment with lutetium Lu 177 dotatate plus long-acting octreotide led to a statistically significant and clinically meaningful improvement in progression-free survival compared with high-dose long-acting octreotide alone in newly diagnosed patients with somatostatin receptor–positive, grade 2 and 3, advanced gastroenteropancreatic neuroendocrine tumors.

First-line treatment with lutetium Lu 177 dotatate (Lutathera; lutetium [177Lu] oxodotreotide) plus long-acting octreotide led to a statistically significant and clinically meaningful improvement in progression-free survival compared with high-dose long-acting octreotide alone in newly diagnosed patients with somatostatin receptor (SSTR)–positive, grade 2 and 3, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), meeting the primary end point of the phase 3 NETTER-2 trial (NCT03972488).¹

A key secondary end point of objective response rate (ORR) was also met. Regarding safety, findings were consistent with the known toxicity profile of lutetium Lu 177 dotatate, and no new or unexpected safety signals were reported.

Detailed findings from NETTER-2 will be presented at an upcoming medical meeting and shared with health authorities.

“These positive results for [lutetium Lu 177 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,” Jeff Legos, executive vice president and global head of Oncology Development at Novartis, stated in a news 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.”

In January 2018, the FDA approved lutetium Lu 177 dotatate for the treatment of patients with SSTR-positive GEP-NETs.²

NETTER-2 was an open-label, multicenter, randomized, controlled phase 3 trial that enrolled patients at least 15 years of age and more than 40 kg of body weight with histologically proven, SSTR-positive, metastasized or locally advanced, inoperable, well differentiated grade 2 or grade 3 GEP-NETs who were diagnosed within 6 months prior to enrollment.³Patients were required to have a Ki67 index of at least 10% and no more than 55%, a Karnofsky performance status of at least 60, and at least 1 measurable site of disease.

Key exclusion criteria included documented progression per RECIST v1.1 criteria to previous treatments for the current GEP-NET at any time prior to randomization, a creatinine clearance of less than 40 mL/min, a hemoglobin concentration of less than 5.0 mmol/L, a white blood cell count of less than 2 x 109/L, a platelet count of less than 75 x 109/L, a total bilirubin of more than 3 times the upper limit of normal, and serum albumin of less than 3.0 g/dL, unless prothrombin time was within the normal range.

Patients were randomly assigned to receive 7.4 GBq/200 mCi of lutetium Lu 177 dotatate once every 8 weeks (+/– 1 week) for 4 total doses plus 30 mg of long-acting octreotide every 8 weeks, or long-acting octreotide alone. Patients in the experimental arm had the option to receive 2 to 4 additional doses of lutetium Lu 177 dotatate following progression, and those in the control arm could receive up to 4 cycles of lutetium Lu 177 dotatate plus long-acting octreotide following progression.

Other secondary end points included disease control rate, duration of response, time to decline of global health status, and safety.

References

Novartis radioligand therapy Lutathera demonstrated statistically significant and clinically meaningful progression-free survival in first line advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). News release. Novartis. September 25, 2023. Accessed September 25, 2023. https://www.novartis.com/news/media-releases/novartis-radioligand-therapy-lutathera-demonstrated-statistically-significant-and-clinically-meaningful-progression-free-survival-first-line-advanced-gastroenteropancreatic-neuroendocrine-tumors-gep-nets
FDA approves new treatment for certain digestive tract cancers. News release. FDA. January 26, 2018. Accessed September 25, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-certain-digestive-tract-cancers
Study to evaluate the efficacy and safety of Lutathera in patients with grade 2 and grade 3 advanced GEP-NET (NETTER-2). ClinicalTrials.gov. Updated July 27, 2023. Accessed September 25, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03972488