Abstract 325P
Background
The addition of Angiotensin receptor blockers (ARBs) like losartan (L) has shown to improve outcomes in small prospective studies in pancreatic ductal adenocarcinomas (PDAC).
Methods
Patients diagnosed with treatment naive locally advanced/metastatic PDAC with ECOG PS 0-1, and adequate end organ function were randomly assigned (1:1) to either mFOLFIRINOX or mFOLFIRINOX plus oral Losartan 50mg per day (mFOLFIRINOX-L). Treatment was continued till progression, significant treatment related adverse events or patient choice. The current unplanned analysis comparing median progression free survival (mPFS) between the two arms was conducted to identify an early signal of efficacy before the trial proceeded to full accrual of phase III design (N = 264), though overall survival was the primary endpoint. Plasma TGF-beta levels were measured at baseline, post cycle 1, and after 4 cycles of chemotherapy in both arms to evaluate the putative action of losartan in PDAC via a reduction in TGF-beta levels.
Results
88 patients were randomized, of whom 85 patients were available for analysis (44-mFOLFIRINOX ; 41 - mFOLFIRINOX-L); the median age was 53 years (30-69); 56 patients (64%) had metastatic PDAC while 32 patients (36%) had locally advanced PDAC. With a median follow up of 16.8 months and 73 PFS events, the Hazard Ratio (HR) was 0.84 (95% CI: 0.51 – 1.85; p= 0.93: mFOLFIRINOX vs mFOLFIRINOX-L). The median PFS, 6 month PFS and 12-month PFS were 8.44 months, 56.8% and 37.2% for mFOLFIRINOX, while it was 7.36 months, 61% and 16.1% for mFOLFIRINOX-L, respectively. 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-beta levels across time points was not significantly different between the two arms (ANOVA P>0.05).
Conclusions
The addition of Losartan to mFOLFIRINOX 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 III design in view of these findings.
Clinical trial identification
CTRI/2021/05/033482.
Legal entity responsible for the study
Institutional Ethics Committee (IEC), IEC1 and Tata Memorial Hospital, Mumbai.
Funding
Institutional support from Tata Memorial Hospital.
Disclosure
All authors have declared no conflicts of interest.