Incorporating nivolumab with preceded gemcitabine and S-1 chemotherapy for patients of metastatic pancreatic cancer: a pilot study.

Pancreatic ductal adenocarcinoma (PDAC) rarely responds to immune checkpoint inhibitors. We conducted a pilot study to investigate chemotherapy followed by the addition of nivolumab in metastatic PDAC with limited tumor burden. A single cycle of gemcitabine (850 mg/m² on days 1 and 8) and S-1 (60-100 mg/day on days 1-12) was administered. Patients who had achieved control of carbohydrate antigen 19-9 (CA 19-9) (a decreased level of CA 19-9 or <10% increased level of CA 19-9 comparing to baseline) were provided adding-on nivolumab (3 mg/kg on days 1, 15, and 29) with the same doses of gemcitabine (on days 1, 8, 22, and 29) and S-1 (on days 1-12 and 22-33). The primary endpoint was response rate (RR). After enrolling seven patients, the study was terminated owing to slow recruitment. Five of the seven patients who completed one cycle of gemcitabine plus S-1 (GS) fulfilled the criteria for CA 19-9 and proceeded to receive nivolumab in addition to GS. One patient demonstrated a partial response, and the other four patients had stable disease (SD). The RR and disease control rate (DCR) for gemcitabine and S-1 plus nivolumab (GSN) were 20% and 100%, respectively. The median progression-free survival (PFS) was 6.3 (95% confidence interval [CI], 0-16.4) months. The median overall survival (OS) was 20.8 (95% CI, 16.4-25.2) months. Two patients who did not receive nivolumab continued the GS regimen; one SD and one progressive disease (PD) were observed with a PFS of 3.5 and 3.0 months, respectively. The most common adverse events (AEs) during the GS phase (n = 7) were grade 1-2 neutropenia (n = 5), skin rashes (n = 4), and fever (n = 3). During the nivolumab adding-on phase (n = 5), one grade 3 and one grade 4 neutropenia were observed. Grade 1-2 mucositis (n = 3) was the most common nonhematological AE. In conclusion, adding nivolumab to chemotherapy in patients who had achieved control of CA 19-9 in metastatic PDAC was feasible. (Registration at ClinicalTrials.gov: NCT04377048).