Jordan D. Berlin, MD
Unprecedented findings from the phase III PRODIGE 24/CCTG PA.6 trial brought great hope to the field of locally advanced, resectable pancreatic cancer. However, topline findings from the phase III APACT trial were less than encouraging, leaving physicians unsure of where to place certain agents, explained Jordan D. Berlin, MD.
Prior to the readout of PRODIGE 24/CCTG PA.6, overall survival (OS) for patients with resectable pancreatic cancer had hovered around 24 to 28 months. Following its results, modified FOLFIRINOX became the standard of care in this setting, having resulted in an OS of 54.5 months.1
Yet the combination of gemcitabine and nab-paclitaxel (Abraxane), a commonly used regimen in the metastatic setting, failed to improve disease-free survival (DFS) versus gemcitabine alone in patients with surgically resected pancreatic adenocarcinoma, according to topline results of APACT.2
However, the combination demonstrated a statistically significant improvement in OS, which served as one of the secondary endpoints.
Moreover, radiation therapy, though a compelling modality, has yet to demonstrate a survival benefit in this setting, said Berlin.
Although systemic therapy has been a focus in the field, certain targets may provide additional insight into the disease that may unleash more potent, and importantly targeted approaches that may be able to infiltrate the stroma.
“There are other potential targets in pancreas cancer,” said Berlin. “This disease is not without targets...we're going to start teasing out the weaknesses of various parts of pancreas cancer.”
In an interview during the 2019 OncLive®
State of the Science Summit™ on Gastrointestinal Malignancies, Berlin, Ingram Professor of Cancer Research, professor of medicine, VICC associate director for clinical research strategy, director, Phase I Program, gastrointestinal malignancies, clinical trials, Department of Medicine, Vanderbilt University Medical Center, shed light on current and future directions in the field of locally advanced pancreatic cancer.
OncLive: Could you discuss the neoadjuvant and adjuvant landscape in locally advanced pancreatic cancer?
: The standard of care for resectable disease remains adjuvant therapy, though there has been a shift toward neoadjuvant therapy in clinical trials. As for adjuvant therapy, the most recent data from the [PRODIGE 24/CCTG PA.6 trial] showed that modified FOLFIRINOX should be the standard of care in patients younger than the age of 80, with an excellent performance status. With this regimen, the dose of irinotecan is reduced, and the 5-flurouracil bolus is dropped. There are no other standards for that group of patients. For patients who aren't in as good shape, gemcitabine monotherapy or gemcitabine/capecitabine are also reasonable options.
Neoadjuvant therapy is probably best to use in patients with locally advanced and or borderline resectable disease. Although we say [these patients are] locally advanced, [these cases almost] never go to resection. Here, neoadjuvant therapy is likely the therapy of choice because you have a better chance of an R0 resection.
The combination of nab-paclitaxel and gemcitabine was not found to improve DFS in the phase III APACT trial. Where does that leave the combination in this space?
I'm on the steering committee for the APACT trial; the combination did not meet the trial’s primary endpoint of DFS. We need to see the mature data. Hopefully, we will see it in the very near future. At the moment, gemcitabine and nab-paclitaxel is not an option for adjuvant therapy.
What ongoing trials have you been following?
I’m following the intergroup trials, which are looking at neoadjuvant therapy. We’re also comparing FOLFIRINOX with gemcitabine/nab-paclitaxel in locally advanced disease.