Summary Background Thirty-five percent of pancreatic cancer patients have unresectable locally advanced pancreatic cancer (LAPC) at diagnosis. Several studies have evaluated systemic chemotherapy with FOLFIRINOX for patients with LAPC. We report a patient-level meta-analysis of LAPC patients treated with FOLFIRINOX as first-line treatment. Methods A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar. Studies evaluating FOLFIRINOX as first-line treatment for LAPC were included. The primary outcome was overall survival (OS) and secondary outcomes included progression free survival (PFS), and grade 3 or 4 adverse events. We collected patient-level data from all studies that reported survival outcomes. The Kaplan-Meier method was used for survival outcomes. Grade 3 or 4 adverse event rates and the percentage of subsequent (chemo)radiation or resection in eligible studies were pooled in a random effects model. Findings Thirteen eligible studies representing 689 patients were included of whom 355 had LAPC. Eleven studies, representing 315 LAPC patients, reported survival outcomes and were eligible for patient-level meta-analysis. The median OS ranged from 10·0 to 32·7 months across studies with a patient-level median OS of 24·2 months [95% CI: 21·6 - 26·8 months]. The median PFS ranged from 3·0 to 20·4 months across studies with a patient-level median PFS of 15·0 months [95% CI: 13·8 – 16·2 months]. In 10 studies representing 490 patients, 296 Grade 3 or 4 adverse events were reported (i.e. 60·4 events per 100 patients). No death was attributed to FOLFIRINOX toxicity. Subsequent treatments included (chemo)radiation (63·5%) and surgical resection (25·9%). Interpretation Patients with LAPC treated with FOLFIRINOX had a median OS of 24·2 months that is far superior to previously reported OS with gemcitabine. Future research should evaluate these promising results in a randomized controlled trial and determine which patients might benefit from (chemo)radiation or a resection after FOLFIRINOX.

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Background FOLFIRINOX therapy for pancreatic ductal adenocarcinoma (PDAC) has been reported to result in objective response rates that are 2–3 fold higher than other regimens. Our goal was to assess response rates and resection rates in locally unresectable (stage III) patients initially treated with induction FOLFIRINOX. Methods The institutional cancer database was queried for patients treated with induction FOLFIRINOX therapy between 2010–2013. Patients were included if they were treated at our institution for stage III PDAC (locally unresectable) that had been adjudicated at a weekly multidisciplinary tumor board. Results One hundred and one patients were identified. The median age was 64 years (range:37–81) and the median follow-up was 12 months (range:3–37). Patients received a median of six cycles of induction FOLFIRINOX(range:1–20). No grade 4–5 toxicity was recorded. At initial restaging(median of 3 months following diagnosis), 23 patients(23%) had developed distant metastases, 15 patients(15%) underwent resection, and 63 patients(63%) proceeded to chemoradiation. Within the group of 63patients who proceeded to chemoradiation(median of 9 months following diagnosis), an additional 16 patients(16%) underwent resection and 5(5%) developed metastases. A partial radiographic response was observed in 29% of all patients, which was associated with the ability to perform resection(p=0.004). The median overall survival within the group who progressed on FOLFIRINOX and the group who did not progress were 11 and 26months, respectively. Conclusion Nearly a third of patients who had been initially identified to have stage III pancreatic carcinoma and had been treated with FOLFIRINOX responded radiographically and underwent tumor resection.

Actual 10-year survival after resection of colorectal liver metastases is 24% with an observed 20% cure rate. Patients with both high clinical risk score and extrahepatic disease have an estimated probability of cure less than 5%. When such factors are identified, strong consideration may be given to preoperative strategies, such as neoadjuvant chemotherapy, to help select patients for surgical therapy.