mFOLFIRINOX Plus Clinical Staging Consideration May Improve OS in PDAC

“Although cancer stage has historically been determined on the basis of anatomic criteria alone, this international cohort study demonstrated that anatomic staging of patients with localized PDAC can be improved by evaluating two readily available clinical characteristics,” according to the study authors.

Patients with pancreatic ductal adenocarcinoma (PDAC) given modified fluorouracil with leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) had independent factors that predicted overall survival including tumor anatomy, CA 19-9, and performance status, according to results from a study published in the Journal of Clinical Oncology.

Based on tumor stage, 18.9% of patients had potentially resectable disease, 28.9% had borderline resectable disease, and 52.5% had locally advanced disease. CA 19-9 was evaluated at baseline and was more than 500 U/mL in 32.5% of patients.

For all patients, the median overall survival (OS) was 21.1 months (95% CI, 19.9-22.2). At 1 year, the OS rate was 78.7% (95% CI, 76.8%-80.6%), at 3 years it was 29.1% (95% CI, 27.1%-31.4%) and at 5 years it was 16.8% (95% CI, 14.9%-18.9%).

Prognostic factors at baseline that were poor for OS included borderline resectable disease (HR, 1.26; 95% CI, 1.06-1.50; P = .01), locally advanced disease (HR, 1.71; 95% CI, 1.45-2.02; P <.001), a CA 19-9 level of over 500 U/mL (HR, 1.36; 95% CI, 1.21-1.52; P = <.001), and a World Health Organization (WHO) performance status of 1 or more (HR, 1.31; 95% CI, 1.16-1.47; P <.001).

“Although cancer stage has historically been determined on the basis of anatomic criteria alone, this international cohort study demonstrated that anatomic staging of patients with localized PDAC can be improved by evaluating two readily available clinical characteristics,” the study authors wrote.

The retrospective study evaluated 1835 patients with localized PDAC between January 1, 2012, and December 31, 2019. This was conducted in conjunction with the Trans-Atlantic Pancreatic Surgery (TAPS) Consortium. Of note, patients could not be enrolled on the trial if they had already received surgery as primary therapy, started with a chemotherapy regimen other than FOLFIRINOX, or were referred after starting FOLFIRINOX.

At the time of diagnosis, hepatopancreatobiliary radiologists determined if patients had tumors that were potentially resectable, borderline resectable, or locally advanced based on the tumor’s anatomic position and relationship to adjacent blood vessels.

After biliary decompression, CA 19-9 levels were evaluated before treatment. If patients did not have CA 19-9 measurement with a normalized bilirubin level, the lowest level within 4 weeks was taken. According to WHO criteria, performance status was assessed and collected after biliary drainage prior to treatment.

The primary end point was OS. The last follow-up was October 22, 2022, and those who assessed OS were not blinded for prognostic factors.

Patients received a median of 6 cycles of treatment, and 49.0% of patients underwent radiotherapy after completion of chemotherapy and restaging. Surgical resection occurred in 38.0% of patients, with 66.1% having an R0 resection. Of note, 59.3% were given adjuvant chemotherapy.

A majority of patients were male (54.6%), and the median age was 64 years. The baseline CA 19-9 level was 208.3 U/mL, and WHO performance statuses included 0 (39.3%), 1 (56.7%), and 2 to 3 (4.0%). The median tumor size was 36.0 mm, and the main tumor location in the pancreas was the head for 66.6% of patients.

“This study has several limitations. First, this composite staging system differs from the American Joint Committee on Cancer [AJCC] staging system as it includes nonanatomic factors, but, as we have described, this system is easy to apply to all patients with pancreatic cancer, unlike the AJCC system which has limited clinical utility in patients who do not undergo pancreatectomy,” wrote the authors. “Second, this is a retrospective study with potential information bias, particularly for the WHO performance status. Third, this study included only patients who started treatment with at least one cycle of mFOLFIRINOX as initial treatment without data on patients who started with other systemic regimens. Although similar staging can be expected for other regimens such as gemcitabine with nab-paclitaxel, this should be investigated in future studies.”

Reference

Dekker EN, van Dam JL, Janssen QP, et al. Improved clinical staging system for localized pancreatic cancer using the ABC factors: a TAPS consortium study. J Clin Oncol. Published online February 5, 2024. doi:10.1200/JCO.23.01311