736PMulticenter, phase II trial of biweekly S-1, leucovorin (LV), oxaliplatin and gemcitabine (SLOG) in metastatic pancreatic adenocarcinoma (mPDAC): Final report of TCOG T1211 study

Background: Our previous studies showed a triplet GOFL regimen consisting of gemcitabine plus modified FOLFOX4 was well-tolerated and moderate active in advanced PDAC, and the feasibility of replacing infusion 5-FU/LV with oral S-1/LV, the SLOG regimen, in a dose-escalating, phase I study. Herein, we report the phase II results of the SLOG in mPDAC patients. Methods: Patients with chemo-naïve mPDAC, ECOG PS 0-1, and 20-75 y/o of age were eligible. Intravenous fixed-rate infusion of 800 mg/m2 gemcitabine followed by 2-hr infusion of 85mg/m2 oxaliplatin on D1 plus oral S-1/LV 35/20 mg/m2, twice daily, D1-D7 were given Q 14 days as a cycle. The primary endpoint was objective response rate (ORR). Simon’s optimal two-stage design was used with estimated p0=25% and p1=40%. Results: Between Jun. 2013 and Oct. 2015, a total of 54 patients were included, with median age of 59 y/o, ECOG PS = 1 in 82%, and the presence of liver metastases in 66.7%. At the cut-off Feb.01, 2017, nine patients remained alive and their median follow-up time was 21.3 months. The ORR was partial response in 22 patients (ORR=40.7%, 95% CI, 28-55%) and stable diseases in 19 patients (35.2%). Long-term disease control rate (stable disease >16 weeks) was 64.8% (95% CI, 51-77%). The median progression-free survival and overall survival was 7.6 (95% CI, 4.4-10.7) and 11.4 (95% CI, 8.1-16.3) months, respectively. One-year and two-year survival rates were 46% and 17%, respectively. The most common treatment-related grade 3-4 adverse events included neutropenia (40.7%), anorexia (14.8%), nausea (11.1%), thrombocytopenia (9.3%), and diarrhea (7.4%). Conclusions: Current study demonstrated SLOG is a highly active regimen with manageable and favorable safety profiles for mPDAC patients. A randomized phase II trial comparing SLOG vs. modified FOLFIRINOX in advanced PDAC patients is ongoing. Clinical trial identification: NCT01415713. Legal entity responsible for the study: Taiwan Cooperative Oncology Group, National Health Research Institutes. Funding: National Health Research Institutes. Disclosure: J-S. Chen: Honoraria: Ono, Eli Lilly, MSD, TTY, Novartis. Y-S. Shan: Honoraria: TTY, PharmaEngine. L-T. Chen: Research funding: Novartis, Merck Serono, TTY, Polaris, SyncorePharm, Pfizer, BMS; Honoraria: Ono, Eli Lilly, MSD, PharmaEngine, TTY, SyncorePharm, Novartis, Astra Zeneca, Ipsen; Patents & royalties: ENO-1 mAb/HuniLife; Membership on any entity’s Board of directors or advisory committees: PharmaEngine. All other authors have declared no conflicts of interest.