Dae Won Kim, MD
Although surgery is a therapeutic option for select patients with pancreatic cancer, many patients present with unresectable disease. Progress made in the neoadjuvant space, however, can improve the resectability of locally advanced pancreatic cancer, said Dae Won Kim, MD.
“In pancreatic cancer, even after curative surgery, the recurrence rate is quite high and prognosis is poor,” said Kim. “There are many trials [with the goal of improving] survival after surgery. Knowing the marginal status is very important; it’s one of the predictive markers of survival after surgery. Our goal with neoadjuvant chemotherapy is to improve margin status and [patient] survival.”
In a phase II randomized trial, investigators evaluated the use of neoadjuvant FOLFIRINOX followed by individualized chemoradiotherapy in patients with newly diagnosed, previously untreated, localized borderline resectable disease, who had an ECOG performance status of 0 or 1 as well as adequate hematologic, renal, and hepatic function.
Thirty-four of 43 patients who planned to receive 8 preoperative cycles of chemotherapy were able to complete all cycles of treatment. Further, 27 patients had short-course chemoradiotherapy, while 17 patients underwent long-course chemoradiotherapy. Out of the 48 patients enrolled in the trial, R0 resection was achieved in 31 patients (65%; 95% CI, 49%-78%). Of the 32 patients who underwent resection, the R0 resection rate was 97% (n = 31).1
Moreover, the median progression-free survival (PFS) among all patients enrolled in the trial was 14.7 months (95% CI, 10.5 to not reached), while the 2-year PFS rate was 43%. The median OS was 37.7 months (95% CI, 19.4 months to not reached), while the 2-year OS rate was 56%. In those who underwent resection, the median PFS was even higher at 48.6 months (95% CI, 14.4 to not reached), while median OS had not been reached. The 2-year PFS rate was 55%, while the 2-year OS was 72%.
As such, investigators concluded that preoperative FOLFIRINOX followed by chemoradiotherapy in patients with borderline resectable pancreatic cancer could lead to high rates of R0 resection as well as a prolonged median PFS and OS.
Meanwhile, in the adjuvant space, investigators evaluated the benefit of adjuvant mFOLFIRINOX versus gemcitabine in patients with resected disease in the phase III UNICANCER GI PRODIGE 24/CCTG PA.6 trial.
Results showed that a median follow-up of 30.5 months, the median disease-free survival (DFS) was 12.8 months in those who received gemcitabine versus 21.6 months in those given mFOLFIRINOX (HR, 0.59; 95% CI, 0.47-0.74). Further, the median OS was 34.8 months versus 54.4 months in the gemcitabine and mFOLFIRINOX arms, respectively (HR, 0.66; 95% CI, 0.49-0.89). Median metastasis-free survival (MFS) was 17.7 months in the gemcitabine arm versus 30.4 months in the mFOLFIRINOX arm (HR, 0.59; 95% CI, 0.46-0.76). Based on these data, investigators concluded that mFOLFIRINOX is not only safe but it significantly improved DFS, MFS, and OS compared with gemcitabine.2
Also in the adjuvant setting, it was reported that the combination of nab-paclitaxel (Abraxane) and gemcitabine did not improve disease-free survival (DFS) versus gemcitabine in patients with pancreatic cancer, according to results of the international, multicenter, open-label, controlled, phase III APACT study (NCT01964430).3
However, the combination did show an OS improvement, reaching nominal statistical significance.
In an interview during the OncLive®
State of the Science Summit™ on Gastrointestinal Malignancies, Kim, a medical oncologist in the Gastrointestinal Oncology Program at Moffitt Cancer Center, highlighted recent advances in the neoadjuvant and adjuvant settings for patients with localized pancreatic cancer.
OncLive®: What trials support the benefit of neoadjuvant therapy in patients with localized pancreatic cancer?
: In borderline resectable disease, there are several data actually showing improved survival after mFOLFIRINOX treatment and also neoadjuvant chemoradiation.
I discussed this in more detail in [my presentation at the State of the Science Summit™]. One of them is a phase II trial where the FOLFIRINOX data actually show an improved rate; it improved margin-negative surgery and was also associated with an improvement in survival.
There was also a trial [that evaluated] FOLFIRINOX and then they used gemcitabine and chemoradiation.
Previously, a phase III randomized study actually showed that around 4% of patients can have resectable disease. [In that trial], they used gemcitabine or gemcitabine plus erlotinib (Tarceva), and then patients received chemoradiation after that.