|Pancreatic cancer is a fatal disease, with a 5-year survival rate of less than 5%. Surgery remains the only curative option, but most patients have metastatic pancreatic cancer (MPC) at the time of diagnosis. Systemic chemotherapy with single-agent gemcitabine has been regarded as a standard treatment for MPC for many years. However, recently, in randomized phase III trials, two regimens, gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX, have shown a clear survival benefit over gemcitabine alone. With the emergence of GnP and FOLFIRINOX, an increasing number of patients with MPC have been given a chance to receive treatment with better survival benefit, but long-term effects of these treatments have yet been unsatisfactory. To develop a more effective treatment regimen, many studies evaluating newer drugs, including molecular targeted agents or immunotherapies, are ongoing worldwide. On the other hand, in the absence of clinical trials that directly compare the effectiveness of GnP and FOLFIRINOX, it is difficult to determine which regimen should be employed for patients with MPC in clinical practice. A recent phase I study conducted by our group suggests that S-1 + irinotecan + oxaliplatin (S-IROX) may be effective in treating MPC, and a large phase III study that compares GnP vs. FOLFIRINOX vs. S-IROX is now underway in Japan. In this session, the current status of systemic chemotherapy for MPC will be discussed.