Dr Smaglo on Selecting Between Frontline Chemotherapy Regimens for Pancreatic Cancer

Brandon G. Smaglo, MD, FACP, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses considerations for choosing between available frontline chemotherapy-based regimens for patients with metastatic pancreatic cancer.

In the treatment of patients with pancreatic cancer, there is no clear clinical rationale for administering both irinotecan and liposomal irinotecan (Onivyde; NALIRI) within the same patient’s treatment journey, as these agents are functionally similar. Smaglo begins. However, it is clinically appropriate for patients to receive both 5-FU–based and gemcitabine-based regimens at different points in therapy, he says. Treatment sequencing should be carefully considered to optimize efficacy and minimize toxicity, he emphasizes.

For patients who receive NALIRIFOX (liposomal irinotecan, oxaliplatin, 5-FU, and leucovorin) or FOLFIRINOX (irinotecan, oxaliplatin, 5-FU, and leucovorin) as frontline therapy, the recommended second-line option is gemcitabine plus nab-paclitaxel, he notes. Conversely, if a patient begins their treatment course with gemcitabine plus nab-paclitaxel, a 5-FU–based regimen should be used in the second-line setting, he explains.

Patient performance status and comorbidities play a crucial role in regimen selection, he adds. Patients with poor performance status or significant comorbidities may not tolerate intensive, 3-drug regimens, such as NALIRIFOX or FOLFIRINOX, he states. For these patients, gemcitabine plus nab-paclitaxel remains an appropriate first-line option, followed by a second-line regimen of 5-FU plus NALIRI to reduce toxicity, according to Smaglo.

For robust frontline patients, FOLFIRINOX or NALIRIFOX are superior to gemcitabine-based therapy and should be the preferred initial treatment choices, he continues. However, regimen selection should be personalized based on potential toxicities, he cautions. For instance, diarrhea, a common AE associated with irinotecan-based therapy, is relatively more pronounced with NALIRI, whereas neuropathy and cytopenias are more prevalent with FOLFIRINOX, largely due to oxaliplatin exposure, he states. Therefore, patients with preexisting neuropathy, such as those with diabetes, may not tolerate FOLFIRINOX well, whereas patients with pancreatic insufficiency and baseline diarrhea may struggle with NALIRI-based regimens, he explains. The goal is to select a regimen that ensures prolonged treatment tolerance and efficacy, anticipating barriers to long-term adherence, he concludes.