Randomized Phase II Study of Consecutive-Day versus Alternate-Day Treatment with S-1 as Second-Line Chemotherapy in Advanced Pancreatic Cancer

Abstract

Objective: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study. Methods: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events. Results: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741–1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044). Conclusion: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified.

Immune Checkpoint Blockade in Combination with Stereotactic Body Radiotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma

“…These results demonstrate similar clinical outcome compared with previous reports of no response with ICI monotherapy (14,15,26) or a 1.5% ORR with dual ICI in advanced PDAC (17). Historically, second-line chemotherapy resulted in a median PFS of 1.8 to 3.1 months and OS of 4.5 to 10.1 months, depending on the regimen used (29)(30)(31)(32)(33)(34)(35). In a phase II trial comparing durvalumab alone versus durvalumab plus tremelimumab in patients with advanced PDAC, the median PFS in both arms was 1.5 months and median OS was 3.6 months with durvalumab alone versus 3.1 months with the combination (17).…”