S195 Comparative Efficacy and Safety of Chemotherapeutic, Targeted, and Immunotherapy Drugs for Pancreatic Ductal Adenocarcinoma Treatment: A Network Meta-Analysis of RCTs

Introduction: Pancreatic ductal adenocarcinoma is a highly aggressive malignancy with a poor prognosis and limited treatment options. Current therapeutic strategies include chemotherapy, targeted therapies, and immunotherapy, but their comparative efficacy and safety remain uncertain. Methods: A systematic search across 5 databases was conducted to identify relevant randomized controlled trials, with study screening performed using Covidence. The network meta-analysis was carried out using the Netmeta package in R, and forest plots and meta-analyses were generated with Stat 18.0. Risk of bias was assessed using the RoB 2.0 tool. Results: Our analysis included 33 randomized controlled trials with a total sample size of 9,239 participants, comprising 5,636 in the treatment group and 3,603 in the control group. The included studies evaluated therapies such as atezolizumab (79), cabozantinib (76), combined chemotherapy (58), demivistat + FOLFIRINOX (266), durvalumab (3), EGPH20 + GEM-NABP (327), erlotinib (518), FOLFIRINOX (433), gemcitabine (2,090), irinotecan (1,216), mitazalimab (70), nab-Paclitaxel (71), nadunolimab (76), napabucasin + GEM-NABP (565), olaparib (124), narilifox (766), placebo (322), and zenocutumab (454). The most significant survival benefit was observed with irinotecan (odds ratio = 4.96, 95% CI [1.45; 16.91]), while the least survival benefit was seen with zenocutumab (odds ratio = 0.38, 95% CI [0.03; 4.41]) compared to placebo. The SUCRA ranking analysis revealed that zenocutumab ranked the lowest in terms of cumulative probability, indicating the worst performance, while irinotecan and cabozantinib exhibited the highest rankings, suggesting superior efficacy compared to other treatments. The risk ratios for adverse events, reflecting safety, were as follows: Neurological consequences 0.47 (95% CI -0.68 to 1.67), Nausea -0.31 (-0.82 to 0.20), HSR 0.28 (0.13 to 0.42), and Death 0.55 (-3.24 to 4.33). Quality of life was significantly improved in irinotecan and cabozantinib treatments. Additionally, the risk of bias was found to be low across all studies included in the analysis. Conclusion: The analysis identifies irinotecan and cabozantinib as promising pancreatic ductal adenocarcinoma treatments, demonstrating significant survival benefits and quality of life improvements. However, further studies are needed to validate these findings and evaluate long-term outcomes across diverse populations.