Eileen M. O’Reilly, MD
Recent developments in the treatment of metastatic pancreatic cancer have modestly improved outcomes, but reducing morbidities associated with current therapies and developing novel therapeutics will be essential for achieving durable responses and long-term survival, according to experts who participated in an OncLive®
The advent of multiagent chemotherapy in the frontline setting and the introduction of an FDA-endorsed option for second-line treatment have increased the choices for treatment of metastatic disease. However, many questions remain on optimal sequencing of therapies, the role of novel therapies such as immunotherapy and stroma-targeting agents, and the use of molecular profiling to personalize treatment.
Furthermore, the panelists agreed that caring for patients with pancreatic cancer requires a multidisciplinary approach that includes a medical team (ie, diagnostics, imaging, surgery, chemotherapy, and radiation therapy) and social services (ie, palliative care, social work, psychiatry, and nutrition). “This is an incredibly life-changing moment for these patients, and we’re going to do everything we can to either cure them or keep them alive as long as possible,” said John L. Marshall, MD. “It’s absolutely a team sport.”
Multiagent Frontline Chemotherapy
Until recently, gemcitabine monotherapy was considered the standard treatment for metastatic pancreatic cancer. Trials showing superior overall survival (OS) with gemcitabine plus nab-paclitaxel (Abraxane)1
—a 4-drug combination of leucovorin, fluorouracil (5-FU), irinotecan, and oxaliplatin—established these 2 regimens as frontline options for patients with metastatic pancreatic cancer and good performance status. Although these 2 combinations have not been directly compared in a head-to-head trial, some experts favor FOLFIRINOX for patients with high performance status because the PRODIGE 4/ ACCORD 11 trial with FOLFIRINOX demonstrated a numerically longer OS than the MPACT trial did with gemcitabine/nab-paclitaxel (11.1 vs 8.5 months).
However, many of the panelists questioned whether the potential increase in survival is worth choosing FOLFIRINOX due to its high toxicity. Marshall said that he starts with gemcitabine/nab-paclitaxel for most of his patients. “I don’t see the added advantage of what may be a small increase in response rate compared with the toxicity,” he said. When Marshall does use FOLFIRINOX, he often drops the bolus dose of 5-FU, lowers the dose of irinotecan to 150 mg/m2
, and gives a growth factor to minimize toxicity. “I don’t really think I could give the standard regimen regularly to people,” he said. “Even with modifications, we all buckle in for what might be a rough cycle or 2 until we get the dosing right.”
Similarly, Eileen M. O’Reilly, MD, said that she feels more comfortable starting with gemcitabine/nab-paclitaxel because there is more evidence supporting its efficacy and because the regimen is “a nice building block” upon which to add second-line agents. However, she and Caio Max S. Rocha Lima, MD, noted that the DNA-damaging agents (oxaliplatin and irinotecan) in FOLFIRINOX may warrant its firstline use for patients with known or suspected BRCA
O’Reilly also pointed out that adverse event profiles for each of the regimens may also merit consideration. For example, some patients may be concerned about having a port and receiving FOLFIRINOX intravenously, whereas others may worry about alopecia with a nab-paclitaxel-based regimen.