Neoadjuvant FOLFIRINOX in patients with (borderline) resectable pancreatic cancer: A systematic review and patient-level meta-analysis.

Abstract

Background: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n ¼ 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] ¼ 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI ¼ 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patientlevel survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI ¼ 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI ¼ 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI ¼ 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI ¼ 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI ¼ 8.1 to 14.2). No deaths were attributed to FOLFIRINOX.

FOLFIRINOX in borderline resectable and locally advanced unresectable pancreatic adenocarcinoma

“… 20 – 22 In patient-level meta-analyses for neoadjuvant FOLFIRINOX, median PFS and OS were 18.0 months and 22.2 months in patients with BRPC, respectively, while median PFS and OS were 15.0 and 24.2 months in patients with LAPC, respectively. 21 , 22 Although our data seems somewhat inferior to the outcomes of these meta-analyses, direct data comparison should be performed with caution due to the heterogeneity that exists even within BRPC and LAPC. This fact is supported by the findings that median PFS and OS ranged from 3.0–20.4 months to 10.0–32.7 months, respectively, among studies included in the meta-analysis.…”

“…Interestingly, there was no difference in survival outcomes between BRPC and LAPC, in line with the results of patient-level meta-analysis. 21 This may indicate that tumor biology, rather than anatomic involvement of major vessels, may be important in patients with BRPC or LAPC treated with FOLFIRINOX.…”

Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

“…Chemotherapy is an important part of PDAC treatment [ 45 ]. It may be applied systemically if the cancer has metastasized or may be combined with surgery in a neo-adjuvant or adjuvant setting [ 1 , 46 ]. Chemotherapy with gemcitabine is the first-line treatment against PDAC and is well tolerated with low side effects [ 42 ].…”

The past, present, and future status of multimodality treatment for resectable/borderline resectable pancreatic ductal adenocarcinoma

“…The effect of NAC-GS suggests control of subdiagnostic liver metastases before surgery for R-PDAC. A systematic review showed that neoadjuvant FOLFIRINOX therapy for BR-PDAC had a favorable median OS, resection rate, and R0 resection rate [60]. The resection rate reached 67.8%, the R0 resection rate was 83.9%, and the median OS ranged from 11.0-34.2 months across studies.…”