By ecancer reporter Janet Fricker

In resected pancreatic adenocarcinoma, adjuvant chemotherapy with a modified FOLFIRINOX led to longer disease free and overall survival than gemcitabine, reports a phase 3 French and Canadian study published in The New England Journal of Medicine.

The incidence of toxicity, however, was higher for FOLFIRINOX.

Although surgery offers the only chance of cure in pancreatic cancer, five-year survival rates following resection are only 10%.

After surgery adjuvant treatment with gemcitabine or fluoropyrimidine has been demonstrated to improve outcomes and is now considered standard of care for resected pancreatic cancer.

However, studies among patients with metastatic pancreatic cancer show combination chemotherapy with FOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) leads to longer overall survival than gemcitabine when administered first-line.

The current PRODIGE 24-ACCORD study set out to explore efficacy of a modified version of the FOLFIRINOX regimen compared with gemcitabine as adjuvant treatment after pancreatic cancer resection.

The modified version of the FOLFIRINOX regimen (without bolus fluorouracil) was designed to decrease toxicity.

Between April 2012 and October 2016 investigators randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma 1:1 to receive modified FOLFIRINOX (n=247) or gemcitabine (n=246).

The study was conducted at 58 hospitals in France and 19 in Canada.

Results at a median follow-up of 33.6 months showed median disease-free survival was 21.6 months with modified-FOLFIRINOX versus 12.8 months with gemcitabine (HR 0.58; P<0.001).

Furthermore, it was shown median overall survival was 54.4 months for the modified-FOLFIRINOX group versus 35.0 months for the gemcitabine group (HR 0.64; P=0.003).

Grade 3 or 4 adverse events occurred in 76% of patients assigned modified-FOLFIRINOX group versus 53 % assigned gemcitabine, but according to the authors side effects were manageable.

One treatment-related death (from interstitial pneumonitis) occurred in the gemcitabine group and none occurred in the modified-FOLFIRINOX group.

“For the first time, our trial shows a large benefit from adjuvant FOLFIRINOX chemotherapy over standard chemotherapy with gemcitabine, showing we can help patients with pancreatic cancer live longer,” said lead author Thierry Conroy, from the Institut de Cancérologie, Lorraine, France.

“In addition, we were encouraged to see the results were better than expected when we planned this trial.”

Conroy made his comments when he presented the results at the 2018 ASCO meeting last June.

Reference: Conroy T, Hammel P, Hebbar M et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. New England Journal of Medicine. 2018, 379 (25): 2395-406.