Autumn McRee, MD
Some of the most encouraging data to be read out in the pancreatic cancer space within the last decade came from the PRODIGE 24/CCTG PA.6 trial, said Autumn McRee, MD, as this was the first trial to demonstrate an overall survival (OS) benefit with an adjuvant strategy of intense chemotherapy combinations often used in the metastatic setting.
In the multicenter phase III trial, patients were randomized to receive either 28-day cycles of the standard gemcitabine on days 1, 8, and 15 for 6 cycles (arm A) or modified FOLFIRINOX every 14 days for 12 cycles (arm B). Disease-free survival (DFS) served as the primary endpoint of the trial, with OS, metastasis-free survival, and adverse events as secondary endpoints.
At a median follow-up of 33.6 months, the median DFS was 12.8 months (95% CI, 11.7-15.2) in arm A versus 21.6 months (95% CI, 17.5-26.7) in arm B.1
Moreover, the median OS was 35.0 months (95% CI, 28.6-43.8) versus 54.4 months (95% CI, 41.5-not reached) in arms A and B, respectively.
“We saw for the first time, an OS of close to 54 months, which is incredibly promising in this patient population,” said McRee, who is an associate professor of medicine at the University of North Caroline (UNC) School of Medicine, UNC-Chapel Hill.
McRee also highlighted studies in which investigators are working to bring strategies used in the postoperative space into the neoadjuvant setting. For example, in the ongoing phase II Alliance for Clinical Oncology Trial A021501 (NCT02839343), investigators are evaluating the efficacy of mFOLFIRINOX with or without stereotactic body radiation therapy before surgery in patients who are borderline resectable. This study has an estimated primary completion date of March 2020.2
In an interview during the 2019 OncLive®
State of the Science Summit™ on Gastrointestinal Malignancies, McRee highlighted promising adjuvant/neoadjuvant strategies under investigation in the pancreatic cancer space and stressed the importance of using a multidisciplinary treatment approach to improve patient outcomes.
OncLive®: What therapies are being explored in the neoadjuvant or adjuvant setting?
: One of the more promising studies that we saw come out of the pancreas space in the last decade was the PRODIGE 24/CCTG PA.6 study, data from which were reported at the 2018 ASCO Annual Meeting. This was, for the first time, an adjuvant strategy comprised of more aggressive chemotherapy combinations that we typically use in the metastatic setting. For this study, [investigators] randomized patients who had been resected to receive either gemcitabine, which is an old standard, to the 3-drug combination FOLFIRINOX. That study followed on the heels of the ESPAC-4 study, which combined gemcitabine with capecitabine.
It is nice now to have options for patients in the postoperative space. Certainly, some [responses] are going to be more robust than others. We reserve FOLFIRINOX more for the patients who come to us with a well-preserved performance status and have recovered uneventfully from their surgery.
However, there are now studies looking to bring those treatments to the neoadjuvant space; [for example, work by] Matthew H.G. Katz, MD, from the Alliance for Clinical Trials in Oncology and The University of Texas MD Anderson Cancer Center.
Could you expand on these studies?
The study that Dr Katz is leading is looking at patients who are borderline resectable, meaning that we are optimistic that they are resectable, but they have certain features of their cancer that make them unlikely to have a complete resection; that is usually intimate involvement of certain blood vessels.