Objectives: Several meta-analyses (MAs) have reported the survival benefits and safety issues of chemotherapy regimens for pancreatic cancer (PC). The aim was to perform an umbrella review to summarize the existing evidence from MAs of randomized controlled trials (RCTs) and to grade the quality of evidence

Methods: EMBASE, PubMed, Cochrane Review, and Epistemonikos were searched from inception to October 31st, 2021, for MAs of RCTs evaluating chemotherapy regimens for PC. Methodological quality was assessed using the A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) tool. The quality of evidence was evaluated by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations).

Results: A total of 2,732 records were screened; of those 306 articles were assessed for eligibility, and 25 articles corresponding to 168 MAs in patients with either resected or advanced PCs were included in the review. Two (8.0%) studies were found to be of high methodological quality. 80 MAs (47.6%) reported the survival benefits of using different combinations of chemotherapy regimens, while 88 MAs (52.4%) reported safety outcomes. 77 (45.8%; 35 for efficacy and 42 for safety outcomes) of the 168 MAs for survival and safety endpoints were statistically significant (P ≤0.05). No MAs were graded as high-quality evidence. 7 MAs reporting the survival benefits of gemcitabine combination regimens were graded as moderate quality of evidence in the main and sensitivity analyses. Only 1 MA comparing the gemcitabine combination regimens (with Nab/Paclitaxel or Capecitabine) versus monotherapy among advanced PC patients was upgraded to high quality after a sensitivity analysis by excluding small-sized studies [progression-free survival; HR = 0.78 (95%CI, 0.69-0.88)]. The remaining MAs were either low or very low quality of evidence.

Conclusion: Our review showed that the use of gemcitabine combination regimens demonstrated survival benefits over gemcitabine monotherapy, which were supported by moderate to high-quality evidence.