Phase III Trial Examines Lanreotide for Prevention of Postoperative Pancreatic Fistula

Postoperative pancreatic fistula (POPF) remains the defining complication of pancreatectomy, leading to significant morbidity, mortality, and increased healthcare costs. Multiple trialed interventions have failed to meaningfully reduce the incidence of POPF.¹

Somatostatin Analogs as Fistula Prophylaxis

Since the early 1990s, numerous studies have explored the role of perioperative somatostatin analogs (SSAs) for POPF prophylaxis. Early trials primarily used octreotide and reported mixed results, and interpretation of study findings is complicated by evolving definitions of POPF over time.²

In 2014, a landmark randomized controlled trial (RCT) by Allen and colleagues demonstrated that perioperative pasireotide, a newer generation SSA, significantly reduced the incidence of POPF in patients undergoing pancreatectomy. The trial reported reductions in POPF rates in patients undergoing both Whipple (10% versus 21%) and distal pancreatectomy (7% versus 23%), but has been criticized due to its single-center design and off-target effects (e.g., nausea, bloating) associated with the drug.³

Lanreotide, a long-acting SSA with a more favorable dosing and side-effect profile has been proposed for use in POPF prophylaxis. In a recent single-arm phase 2 trial conducted at the University of Washington in Seattle, a single dose of preoperative lanreotide was associated with POPF rates of 11% in patients undergoing pancreaticoduodenectomy and 3% for distal pancreatectomy, both significantly lower than institutional and published historical rates.^1,2,4

Interestingly, in both the pasireotide and lanreotide studies, SSA administration was associated with a greater effect in patients undergoing distal pancreatectomy (as opposed to pancreaticoduodenectomy). This relationship has been observed in other studies, including a meta-analysis of 18 trials evaluating multiple perioperative SSAs, showing a relative risk for developing POPF of 0.41 in patients undergoing distal pancreatectomy, compared to 0.87 in patients undergoing pancreaticoduodenectomy. Researchers  concluded that “further RCTs are urgently needed to investigate the effect of somatostatin analogues after distal pancreatectomy.”²

Latest Trial Seeks to Improve Outcomes

SWOG 2408 (NCT06807437) is a multicenter, phase III randomized controlled trial sponsored by the National Cancer Institute (NCI) Division of Cancer Prevention comparing the incidence of POPF in participants undergoing distal pancreatectomy who receive a single dose of preoperative lanreotide (120 mg subcutaneous) versus placebo (see Figure below). Participants must be planning to undergo elective distal pancreatectomy for a malignancy or lesion with malignant potential within 60 days of registration. Planned enrollment of 274 eligible participants will take place at academic and community sites in the US and Canada.

Due to recent data suggesting differential rates of POPF with the use of postsurgical drains,⁵ postoperative drain use is optional, and participant randomization will be stratified by each surgeon's planned placement of a drain at the time of registration. Secondary study endpoints include comparing rates of biochemical leak, number of postoperative hospital days, and cancer-specific quality-of-life metrics (EORTC QLQ-C30). Other pancreatectomy-related complications such as delayed gastric emptying, post-pancreatectomy hemorrhage, and time to initiation of chemotherapy will be evaluated as exploratory endpoints.

Inclusion criteria are intentionally broad in an attempt to perform a pragmatic, generalizable trial. Any patient with a histologic or radiographic diagnosis of pancreas malignancy or a lesion with malignant potential is potentially eligible. Common clinical diagnoses may include pancreas ductal adenocarcinoma, pancreatic neuroendocrine tumor, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. Notable exclusion criteria include planned multivisceral resection (e.g., partial gastrectomy, modified Appleby-type procedure), treatment with a SSA within the prior 180 days, previous radiation therapy to the pancreas, a history of peptide receptor radionuclide therapy, and a primary diagnosis of pancreatitis (without suspicion of malignancy).

Opportunity to Improve

Researchers participating in the SWOG 2408 trial aim to bring clarity to the role of SSAs in POPF prophylaxis through a straightforward study targeting participants most likely to benefit from the intervention. The study was activated in February 2025 and is open to all participants of the NCI National Clinical Trials Network and the NCI Community Oncology Research Program sites.

For more information, contact national study chair Dr. Jonathan Sham at jsham@uw.edu.

Disclaimer

The thoughts and opinions expressed in this column are solely those of the authors and do not necessarily reflect those of the ACS.

Dr. Shahmir Chauhan is a research fellow in the Department of Surgery at the University of Washington in Seattle.

References

1. Chauhan SSB, Vierra B, Park JO, Pillarisetty VG, et al. Prophylactic somatostatin analogs for postoperative pancreatic fistulas: A cross-sectional survey of AHPBA surgeons. HPB (Oxford). 2024;26(10):1229-1236.
2. Schorn S, Vogel T, Demir IE, et al. Do somatostatin-analogues have the same impact on postoperative morbidity and pancreatic fistula in patients after pancreaticoduodenectomy and distal pancreatectomy? – A systematic review with meta-analysis of randomized-controlled trials. Pancreatology. 2020;20(8):1770-1778.
3. Allen PJ, Gönen M, Brennan MF, et al. Pasireotide for postoperative pancreatic fistula. N Engl J Med. 2014;370(21):2014-2022.
4. Pillarisetty VG, Abbasi A, Park JO, Sham JG. A phase II trial of lanreotide for the prevention of postoperative pancreatic fistula. HPB (Oxford). 2022;24(11):2029-2034.
5. Vissers FL, Balduzzi A, van Bodegraven EA, et al. Prophylactic abdominal drainage or no drainage after distal pancreatectomy (PANDORINA): A study protocol of a binational multicenter randomized controlled trial. Trials. 2022;23(1):809.