Retrospective Analysis of CA19-9 Decrease in Patients with Metastatic Pancreatic Carcinoma Treated with FOLFIRINOX or Gemcitabine in a Randomized Phase III Study (ACCORD11/PRODIGE4)

Abstract

Objectives: Carbohydrate antigen 19-9 (CA19-9) is a sensitive and specific serum marker in pancreatic cancer. Our retrospective analysis aims to evaluate CA19-9 decrease in patients with metastatic pancreatic cancer treated in ACCORD11/PRODIGE4 (FOLFIRINOX vs. gemcitabine). Methods: A total of 342 patients were treated. CA19-9 was measured at 8 weeks (±2) in 160 patients from a total of 282 with abnormal CA19-9 values at baseline (gemcitabine arm, n = 75; FOLFIRINOX arm, n = 85). In the present study, 8-week CA19-9 decrease or greater CA19-9 decrease according to the 20 and 90% thresholds were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated in each subgroup. Results: In the FOLFIRINOX arm, patients with an 8-week CA19-9 decrease or greater CA19-9 decrease ≥20% showed improved median OS, PFS, and objective response rate. In the overall study population, median OS and PFS were significantly improved in patients with an 8-week CA19-9 decrease ≥20% (vs. <20%). The 8-week CA19-9 decrease was predictive of PFS (interaction test significant according to treatment arm; p = 0.006). Conclusion: An 8-week CA19-9 decrease ≥20% is a prognostic factor for OS and PFS. The 8-week CA19-9 decrease (20% threshold) is predictive of PFS. It could help to evaluate the efficacy of FOLFIRINOX and gemcitabine regimens.

Prognostic and predictive factors in pancreatic cancer

“…Despite its approval, it is far to be an ideal prognostic biomarker: it can yield false negative results in patients who do not express the Lewis blood antigen, accounting from 5% to 10% of general population [82], as it can give false positive results in case of pancreatitis, cholestasis, diabetes, cirrhosis or other cancers [82]. Many studies described the prognostic role of CA19-9 decline after curative surgery [84] and during chemotherapy [85,86], especially an early decrease during treatment has been supposed to foresee a longer PFS [87] in patients receiving gemcitabine-nabpaclitaxel and FOLFIRINOX. Conversely there are also data that do not support these findings [88].…”

“…In patients treated in ACCORD11/PRODIGE4 trial, an early (8 weeks) CA19-9 decrease with respect to 20% was predictive of better PFS and could help to evaluate the efficacy of chemotherapy regimen such as FOLFIRINOX or gemcitabine [87].…”

Lewis antigen‑negative pancreatic cancer: An aggressive subgroup

“…Carbohydrate antigen 19-9 (CA19-9), also called sialyl Lewis antigen A, is the most important biomarker for pancreatic cancer (6)(7)(8). The sensitivity in detecting pancreatic cancer is ~80% for CA19-9 (9).…”

Response to Preoperative Therapy in Localized Pancreatic Cancer

“…The decrease of CA 19-9 after chemotherapy was also investigated as a part of the ACCORD/PRODIGE4 trial, comparing FOLFIRINOX to gemcitabine in 160 metastatic patients. Patients with a CA 19-9 ≥20% had an overall response rate significantly higher than patients with CA 19-9<20% (44 vs. 22.9%) (42).…”