A meta-analysis and systematic review of randomized controlled trials in combination Gemcitabine with Erlotinib in the pancreatic cancer

Abstract

Abstract Background and aim: Previous studies have demonstrated the efficacy and safety of combining Gemcitabine and Erlotinib (Gem-Erlo) for the treatment of pancreatic cancer (PaC). However, there is a limited number of clinical studies and multiple prospective randomized controlled clinical trials (RCTs) have yielded inconsistent conclusions. The question of whether Gem-Erlo has significant advantages over conventional chemotherapy in the treatment of PaC has been controversial. In order to provide valuable insights for PaC treatment, this study conducted a meta-analysis based on the current evidence from RCTs. Method: We searched several databases including PubMed/Medline, Web of Science, Cochrane Library, and Embase, as well as relevant conference abstracts from the beginning of their inception to July 2023. We used the patient/population, intervention, comparison, outcomes and study design (PICOS) principle to screen the literature. After title, abstract and full text filtering, we extract the data from each study to assess the risk of bias by examining the quality of the literature. We used a meta-analysis with random effects model to synthesize and summarize the results regarding objective response rate (ORR), disease control rate (DCR), median progression-free survival (median PFS), median overall survival (median OS) and one-year survival rate. Results: Seven RCTs were included, involving 2,152 PaC patients treated with either Gem-Erlo or Gemcitabine alone. The results showed that Gem-Erlosignificantly improved DCR (DCR = 1.74; 95% CI=[1.03, 2.92]; P = 0.04); but did not significantly improve median OS (SMD = −0.20; 95%CI=[−1.46, 1.06]; P = 0.75), median PFS (SMD = −0.97; 95%CI=[−4.01, 2.07]; P = 0.53), ORR (ORR = 1.29; 95%CI=[0.84, 1.97]), or one-year survival rate (ORR = 1.18; 95%CI=[0.88, 1.57]). The most common adverse events (AEs) were rash, diarrhea, fatigue, neutropenia and thrombocytopenia in both groups, but the Gem-Erlo group is more often than the Gemcitabine alone (ORR = 1.40, 95% CI= [1.19, 1.65]; P < 0.0001), and all AEs were within the acceptable range for patients. Conclusion: Gem-Erlo can improve DCR when compared to Gemcitabine. There was no statistically significant improvement in median PFS, median OS, ORR and one-year survival rate. However, sensitivity analysis showed a statistical difference in the median OS. Our study indicated that Gem-Erlo had better efficacy than Gemcitabine alone in PaC therapy. The occurrence of AEs is under the acceptable range for patients.