Meta-analysis of FOLFIRINOX-based neoadjuvant therapy for locally advanced pancreatic cancer

Currently, the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is the standard therapy for metastatic pancreatic cancer. In recent years, FOLFIRINOX-based neoadjuvant therapy for locally advanced pancreatic cancer (LAPC) has been gaining an increasing amount of attention, owing to its ability to reduce disease stage and transform LAPC to borderline resectable or even resectable pancreatic cancer. Accordingly, we aimed to evaluate the efficacy of first-line FOLFIRINOX chemotherapy in patients with LAPC. We searched PubMed, Embase, and Cochrane Library from the time of establishment till January 1, 2020 and included studies focusing on LAPC patients who received FOLFIRINOX as first-line neoadjuvant treatment. The primary outcomes were: resection rate and radical (R0) resection rate while the secondary outcomes were: objective response rate, overall survival, progression-free survival, and rate of grade 3 to 4 adverse events. The meta package for R 3.6.2 was used for heterogeneity and publication bias testing. Twenty-one studies, including 653 patients with LAPC, were selected. After treatment with FOLFIRINOX, the resection rate was 26% (95% confidence interval [CI] = 20%–32%, I2 = 61%) and R0 resection rate was 88% (95% CI = 78%–95%, I2 = 62%). The response rate was 34% (95% CI = 25%–43%, I2 = 56%). The median overall survival and progression-free survival durations ranged from 10.0 to 32.7 months and 3.0 to 25.3 months, respectively. The observed grade 3 to 4 adverse events were neutropenia (20.0 per 100 patients, 95% CI = 14%–27%, I2 = 75%), febrile neutropenia (7.0 per 100 patients, 95% CI = 5%–9%, I2 = 42%), thrombocytopenia (6.0 per 100 patients, 95% CI = 5%–8%, I2 = 27%), nausea/vomiting (7.0 per 100 patients, 95% CI = 7%–12%, I2 = 76%), diarrhea (10.0 per 100 patients, 95% CI = 8%–12%, I2 = 38%), and fatigue (9.0 per 100 patients, 95% CI = 7%–11%, I2 = 43%). FOLFIRINOX-based neoadjuvant chemotherapy has the potential to improve the rates of resection, R0 resection, and median OS in LAPC. Our results require further validation in large, high-quality randomized controlled trials.