Background: We performed a critical overview of published systematic reviews (SRs)
of chemotherapy for advanced and locally advanced pancreatic cancer, and evaluated their quality
using AMSTAR2 and ROBIS tools.
Materials and Methods: PubMed and Cochrane Central Library were searched for SRs on 13th
June 2020. SRs with meta-analysis which included only randomized controlled trials and that had
assessed chemotherapy as one of the treatment arms were included. The outcome measures, which
were looked into, were progression-free survival (PFS), overall survival (OS), and adverse events
(AEs) of grade 3 or above. Two reviewers independently assessed all the SRs with both ROBIS
Results: Out of the 1,879 identified records, 26 SRs were included for the overview. Most SRs had
concluded that gemcitabine-based combination regimes, prolonged OS and PFS, but increased the
incidence of grade 3-4 toxicities when compared to gemcitabine monotherapy, but survival benefits
were not consistent when gemcitabine was combined with molecular targeted agents. As per
ROBIS, 24/26 SRs had 'high' risk of bias, with only 1/26 SR having 'low' risk of bias. As per AMSTAR2,
25/26 SRs had 'critically low', and 1/26 SR had 'low' confidence in the results. The study
which scored 'low risk of bias' in ROBIS scored ‘low confidence in results’ in AMSTAR2. The inter-
rater reliability for scoring the overall confidence in the SRs with AMSTAR2 and the overall
domain in ROBIS was substantial; ROBIS: kappa=0.785, SEM=0.207, p<0.001; AMSTAR2: kappa=
0.649, SEM=0.323, p<0.001.
Conclusion: Gemcitabine-based combination regimens can prolong OS and PFS but also worsen
AEs when compared to gemcitabine monotherapy. The included SRs have an overall low methodological
quality and high risk of bias as per AMSTAR2 and ROBIS respectively.