Dr Dietrich on the Limitations of Chemotherapy in Pancreatic Cancer

“[Although chemotherapy] may be effective immediately, the [main] concern is durability. [This is] not only from an efficacy standpoint, but [in regards to] cumulative toxicity.”

Martin F. Dietrich, MD, PhD, a medical oncologist at The US Oncology Network Cancer Care Centers of Brevard and an assistant professor of internal medicine at the University of Central Florida College of Medicine, discussed the limitations of frontline chemotherapy for the treatment of patients with advanced/metastatic pancreatic cancer.

The current first-line standard of care for patients with advanced/metastatic pancreatic cancer remains chemotherapy, Dietrich began. As multiple chemotherapy regimens can be used in this setting, these must be personalized to the individual patient; accordingly, chemotherapy selection should account for factors such as performance status and organ function, he added.

One standard regimen is gemcitabine plus nab-paclitaxel (Abraxane), Dietrich said. Although this regimen is mild in terms of toxicity, it often has limited efficacy, with an overall response rate (ORR) between 20% and 25%, a median progression-free survival (PFS) of approximately 6 months, and a median overall survival (OS) of less than 1 year, he noted.

Two triplet regimens are also available for this patient population, Dietrich said. mFOLFIRINOX (irinotecan plus oxaliplatin, leucovorin, and 5-fluorouracil [5-FU]) has previously demonstrated efficacy in terms of ORR, PFS, and OS, he added. Recently, data from the phase 3 NAPOLI 3 study (NCT04083235) demonstrated that NALIRIFOX (irinotecan liposome [Onivyde] with oxaliplatin, 5-FU, and leucovorin) produced an ORR of 41.8% (95% CI, 36.8%-46.9%), he noted.

Dietrich emphasized that there are presently no targeted therapies available in the frontline setting and that the chemotherapy approaches, although initially effective, have a limited durability of response. Toxicity concerns can also arise with chemotherapy regimens, including cumulative neuropathy and cytopenias for gemcitabine plus nab-paclitaxel, and neurotoxicity for the triplets, he said. Overall, there is a lot of room for improvement in frontline, advanced/metastatic pancreatic cancer, and many patients do not qualify for treatment at all, he concluded.