Efficacy of losartan plus modified FOLFIRINOX versus modified FOLFIRINOX in advanced pancreatic cancers: A randomized clinical trial (AFPAC Study).

Background: The addition of angiotensin receptor blockers like losartan (L) has been shown to improve outcomes in small prospective studies of pancreatic ductal adenocarcinomas (PDAC).

Methods: Patients diagnosed with treatment-naive locally advanced/metastatic PDAC with Eastern Cooperative Oncology Group performance status 0-1 and adequate end- organ function were randomly assigned (1:1) to either chemotherapy (mFOLFIRINOX or mFOLFIRINOX plus oral losartan 50 mg per day). The current unplanned analysis was conducted to identify an early signal of efficacy. Plasma TGF-β levels were measured at baseline, post cycle 1, and post cycle 4 in both arms.

Results: With a median follow-up of 16.8 months, a total of 88 patients were randomized in the mFOLFIRINOX and mFOLFIRINOX-L arms (44 patients per arm). The number of deaths at 6 months, 6-month overall survival (OS), and median OS was 12, 72.7% (95% confidence interval [CI], 59.3-86.1), and 10.4 months versus 11, 73.2% (95% CI, 59.4-87), and 9.1 months, respectively, with a hazard ratio of 0.76 (95% CI, 0.47-1.22, p = .392). There were no differences in response rates (22% vs. 23%) between the mFOLFIRINOX and FOLFIRINOX-L arms, respectively. Nine patients (22%; n = 41) required temporary cessation of losartan due to accompanying chemotherapy-related adverse events. The trend of plasma TGF-β levels across time points was not significantly different between the two arms (ANOVA p > .05).

Conclusions: The addition of losartan to mFOLFIRINOX in the AFPAC study did not provide an early signal of efficacy in improving progression-free survival in advanced PDAC. The trial will not proceed to full accrual of phase 3 design.