Using PRRT with 177Lu-DOTATATE before surgery is both safe and effective for patients with non-functioning pancreatic neuroendocrine tumors and certain risk factors, according to the results of the NEOLUPANET trial.
The Phase II study reported a 58% rate of partial tumor reduction, stable disease in the remaining patients, and no cases of tumor progression.
Non-functioning PanNETs can be challenging to treat, with surgery being the primary curative therapy. However, patients at high risk of recurrence after surgery might benefit from pre-surgical therapies.
Lu 177 DOTATATE is a type of peptide receptor radionuclide therapy or PPRT. PRRT using Lu-177 DOTATATE treats NETs by converting a cancer cell’s unique characteristics into a welcome mat for a “Trojan Horse” packed with cancer-killing radiation. The therapy was approved for use in the United States in January 2018.
The multicenter NEOLUPANET trial included 31 patients with resectable or potentially resectable non-functioning PanNETs and risk factors for recurrence who received up to four cycles of 177Lu-DOTATATE prior to surgery. The primary objective was to assess safety by tracking complications and mortality within 90 days after surgery.
In this study, “high risk” included certain features that made a patient’s tumor more concerning or difficult to treat:
- Tumor size larger than 4 cm
- Rapid tumor growth (measured by the Ki-67 index)
- Tumor spreading to nearby organs or blood vessels
- Blood clots in certain veins near the pancreas
- A single, removable spot of cancer in the liver
- Enlarged lymph nodes that show cancer activity on special imaging tests
The study team, led by Stefano Partelli at the School of Medicine, Vita-Salute San Raffaele University in Milan, Italy, found that 18 participants experienced a partial reduction in tumor size, and 13 patients had stable disease. No tumor growth was observed in any study participant. Additionally, 28 of 29 participants successfully underwent tumor resection, with most achieving complete removal of the tumor.
While 72% of participants experienced some form of post-surgical complications, the investigators reported that only 7 had severe complications, and no participants died. Although the neoadjuvant therapy did not reduce the overall rate of surgical complications, it demonstrated that 177Lu-DOTATATE is a safe and viable option for pre-surgical treatment in patients with NF-PanNETs. These results suggest that this approach could help improve surgical outcomes and reduce disease progression risks, especially in patients with aggressive tumor characteristics.
The findings pave the way for further research into optimizing pre-surgical treatments for non-functioning PanNETs and improving long-term patient outcomes.