Sequence Therapy with FOLFIRINOX and Gemcitabine/Nab-Paclitaxel for Patients with Advanced Pancreatic Cancer: A Monocentre Retrospective Cohort Study.

BACKGROUND AND AIMS

While irresectable pancreatic cancer has still a dismal overall prognosis, evidence about the optimal chemotherapy sequence is scarce. After treatment with FOLFIRINOX in first-line, gemcitabine monotherapy was established for years. As a potential treatment alternative after failure of FOLFIRINOX therapy, combination of gemcitabine and nab-paclitaxel is used. However, this combination has formally not yet been approved for second-line treatment and investigation of efficiency and treatment tolerance is the aim of this trial.

METHODS

Therefore, we investigated 225 patients with histologically confirmed local advanced or metastatic pancreatic cancer in this retrospective monocentre study (November 2010 - July 2019). Of this, 44 patients received FOLFIRINOX therapy and outcome was further analysed. The primary end point of this cohort was overall survival (OS), and secondary end points included progression-free survival (PFS), response rate, and safety.

RESULTS

In most of the patients, FOLFIRINOX as first-line treatment of irresectable pancreatic cancer resulted in temporary cancer control (partial response [PR]: 50% and stable disease [SD]: 18%), whereas tumour progression was observed in 23% of the patients. The median PFS time for FOLFIRINOX treatment was 7.3 months and median OS 10.3 months. Seven (16%) patients received additional local radio chemotherapy of the pancreatic tumour. During first-line therapy, in 8 (18%) patients, laparotomy was performed to proof resectability of the tumour. Hereby, in 3 patients R0- and in 3 patients R1 resection was achieved, whereas 2 patients stayed irresectable. Twenty-five of the 44 patients (57%) received second-line therapy, namely, 24 patients gemcitabine/nab-paclitaxel and 1 patient gemcitabine and erlotinib. Hereby, gemcitabine/nab-paclitaxel led again to temporary tumour control in 46% of the patients (PR: 21%, SD: 25%), while in 29% of the patients, disease progression was observed. Corresponding median PFS for gemcitabine and nab-paclitaxel treatment was 3.5 months. Patients who received second-line treatment with nab-paclitaxel and gemcitabine had a more favourable prognosis (median OS: 17 vs. 9.2 months; HR 0.32 [0.14-0.70], p < 0.001) than patients who were not eligible for second-line treatment. Moreover, in multivariate analyses association with patients' survival and tumour response to chemotherapy in both therapeutic lines and µGT concentrations below 100 IU/L in first-line FOLFIRINOX chemotherapy were observed.

CONCLUSION

These real-world data suggest that gemcitabine/nab-paclitaxel may be feasible after FOLFIRINOX therapy in patients with irresectable pancreatic cancer. However, prospective randomized data about the superiority to gemcitabine monotherapy are needed.