Expanding Therapeutic Options in Pancreatic Cancer and GEP-NETs Highlight the Need for Refined Patient Selection

Recent advances in the pancreatic cancer and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) spaces are expanding frontline treatment options and introducing novel targeted strategies, necessitating refined approaches to patient selection, according to Shubham Pant, MD, MBBS.

In an interview with OncLive® following a recent State of the Science Summit™ on Gastrointestinal Malignancies, Pant highlighted several of these developments, including the expansion of the frontline metastatic pancreatic cancer arsenal with the February 2024 FDA approval of NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil [5-FU], and leucovorin) and emerging data showing efficacy with peptide receptor radionuclide therapy (PRRT) for metastatic GEP-NETs.¹

One PRRT of note is 177 Lutetium edotreotide (ITM-11; 177Lu-edotreotide). In the phase 3 COMPETE trial (NCT03049189), the targeted radiotherapeutic met the study’s primary end point of improved progression-free survival vs everolimus (Afinitor) in patients with inoperable, progressive, grade 1/2 GEP-NETs.² 177Lu-edotreotide was also well tolerated with a favorable safety profile.

“It's an exciting new era in pancreatic cancer,” Pant, who served as chair of the meeting, emphasized. “Right now, we are looking at these relatively newer therapeutics, and we are still trying to figure out the right patient selection and criteria. These drugs are not without adverse effects, so we are simply learning a lot more as we move into the future.”

Pant is a professor in the Department of Gastrointestinal (GI) Medical Oncology and director of Clinical Research at The University of Texas MD Anderson Cancer Center in Houston.

OncLive: How has the FDA approval of NALIRIFOX affected first-line treatment selection in metastatic pancreatic cancer? How should clinicians weigh certain factors and different results in molecular testing when navigating treatment strategies in this space?

Pant: The [approval of] of NALIRIFOX was [supported by data from] from [the phase 3] NAPOLI 3 study [NCT04083235], which compared [NALIRIFOX] with gemcitabine plus nab-paclitaxel [Abraxane]. That study showed an improvement in overall survival of approximately 2 months, and the regimen was FDA approved.

The other regimen we use frequently in pancreatic cancer is FOLFIRINOX [leucovorin, 5-FU, irinotecan, and oxaliplatin], in which we use standard irinotecan instead of the liposomal version. One of the big differences between these 2 regimens is that NALIRIFOX uses a lower dose of oxaliplatin, at 60 mg/m². Oxaliplatin is a drug that causes neuropathy, so this lower dose can help patients who are at risk for developing that condition. That is one of the key distinctions between those 2 regimens.

What are the potential advantages of PRRT therapies for patients with metastatic GEP-NETs based on data from the COMPETE study?

PRRT therapies are a newer therapeutic option for our patients with NETs. They are showing efficacy compared with the standard of care, which is octreotide or lanreotide. Patients typically receive a few doses—specifically, 4 doses—followed by monitoring for disease control. One of the topics that came up in our recent State of Science Summit was identifying the ideal candidate for this treatment. Honestly, because many NETs are such slow-growing tumors, you could essentially keep patients on a drug like lanreotide for some time. They might not immediately need a more aggressive therapy, especially considering there is a 2% to 3% risk of leukemia with some of these PRRT therapies. We should keep that in mind as a balance.

In which clinical scenarios would you favor the use of cabozantinib (Cabometyx) over PRRT for patients with progressive GEP-NETs? How do real-world challenges like dose adjustments for toxicity and patient adherence affect their translation into real-world practice?

Overall, multiple different radionuclide therapies were discussed at our State of Science Summit. [With PRRT] we thought there would be an access issue, but there is increasing access to PRRT therapies [in clinical practice]. Those are being used in patients who may have more aggressive disease or a higher burden of disease. [Additionally, the question of] whether these therapies translate perfectly from phase 3 trials into practice is still to be decided.

References

1. FDA approves irinotecan liposome for first-line treatment of metastatic pancreatic adenocarcinoma. FDA. Updated February 16, 2024. Accessed March 31, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-irinotecan-liposome-first-line-treatment-metastatic-pancreatic-adenocarcinoma
2. ITM announces positive topline results of phase 3 COMPETE trial with ITM-11, a targeted radiopharmaceutical therapy, in patients with grade 1 or grade 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). News release. ITM Isotope Technologies Munich SE. January 28, 2025. Accessed March 31, 2026. https://www.itm-radiopharma.com/news/press-releases/press-releases-detail/ITM_Announces_Positive_Topline_Results_of_Phase_3_COMPETE_Trial_with_ITM-11,_a_Targeted_Radiopharmaceutical_Therapy,_in_Patients_with_Grade_1_or_Grade_2_Gastroenteropancreatic_Neuroendocrine_Tumors_-GEP-NETs--684/
3. ITM announces FDA acceptance of new drug application (NDA) and PDUFA date for n.c.a. 177Lu-edotreotide (ITM-11) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). News release. ITM Isotope Technologies Munich SE. November 13, 2025. Accessed March 31, 2026. https://www.itm-radiopharma.com/news/press-releases/press-releases-detail/itm-announces-fda-acceptance-of-new-drug-application-nda-and-pdufa-date-for-n-c-a-177lu-edotreotide-itm-11-in-gastroenteropancreatic-neuroendocrine-tumors-gep-nets-747/