Neoadjuvant treatments for resectable (RPC) and borderline resectable pancreatic adenocarcinoma (BRPC): A pairwise and network meta-analysis (NMA).

e16448 Background: Pancreatic adenocarcinoma prognosis is dismal despite the therapeutic advances so far. The only curative chance is represented by surgery, however only a minority of patients (pts) are eligibile for this approach. Evidence on neoadjuvant treatment (NAT) is inconclusive due to significant variability in chemotherapy (CT) or chemoradiotherapy (CRT) regimens and timing. Methods: A systematic review included prospective clinical trials assessing NAT for RPC and BRPC. Studies focused exclusively on locally advanced pancreatic cancer (LAPC) were excluded. A pairwise meta-analysis was conducted to evaluate the impact of different NAT strategies on radical resection (R0) rates, using a random-effects model. A frequentist NMA was performed, with upfront surgery as the reference for R0 rate analysis. P-scores were calculated to rank treatments. The correlation between R0 rates and median Overall Survival (mOS) in RPC pts was assessed using the Spearman correlation coefficient (r). Results: Out of 631 records, 42 studies were included, enrolling 1,888 RPC and BRPC pts treated with upfront surgery (A, 11 trials), FOLFIRINOX (FFX) (B, 8 trials), gemcitabine+nab-paclitaxel (GnP) (C, 7 trials), other triplet CT (D, 2 trials), other doublet CT (E, 5 trials), CRT (F, 12 trials), CT+CRT (G, 10 trials), or gemcitabine monotherapy (H, 1 trial). The pooled R0 rate was 68.8% (95%CI: 61.9-75.0; heterogeneity I^2 80.3%[74.9-84.5]), with significant difference in R0 rates (p < 0.0021) based on treatment type (Table1). The NMA included 12 studies (912 pts). FFX (odds ratio (OR) 2.05, 95%CI: 1.14-3.66, p = 0.016, P-score:0.6383) and CRT (OR 3.18, 95%CI: 1.65-6.10, p < 0.001, P-score:0.9107) significantly improved R0 rate compared with upfront surgery. GnP showed a trend toward improvement(OR 2.03, 95%CI: 0.97-4.23, p = 0.059, P-score:0.6425), but without statistical significance. The pooled R0 rates were 66.3% (95%CI: 54.4-76.4) for BRPC and 65.4% (95%CI: 55.6-74.1) for RPC. Among RPC pts (5 studies, 419 pts), only those treated with FFX (OR 2.12, 95%CI: 1.08-4.15, p = 0.0284) and GnP (OR 2.80, 95%CI: 1.15-6.83, p = 0.024) had significantly improved R0 rates. No correlation was observed between R0 rates and mOS, regardless of the treatment approach (r: -0.232, p 0.405) or individual treatment arms (r:-0.219, p = 0.544). Conclusions: NAT demonstrates efficacy in BRPC pts, yet its role in RPC remains uncertain, as higher R0 rates achieved through NAT do not appear to correlate with improved survival outcomes. R0 rates according to treatment. Arm N° of pts (N° of trials) R0 rate (%) 95% CI A- Surgery 419 (11) 39.6 28.0-52.5 B- FFX 281 (8) 70.5 55.7-81.8 C- GnP 239 (7) 74.6 63.6-83.1 D-other CT (triplet) 72 (2) 78.8 55.5-91.7 E-other CT (doublet) 160 (5) 70.1 48.6-85.3 F-CRT 391 (12) 73.7 60.0-83.9 G-CT + RT/CRT 317 (10) 81.4 69.1-89.5 H-Gemcitabine 9 (1) 77.8 42.1-94.4