Efficacy and safety of EGFR monoclonal antibody combined with gemcitabine-based chemotherapy in first-line treatment of locally advanced unresectable or metastatic pancreatic cancer

The prognosis for patients with advanced pancreatic cancer (PC) remains extremely poor, underscoring the critical need to explore and optimize systemic treatment strategies. This study aimed to evaluate the efficacy and safety of combining EGFR monoclonal antibodies (Anti-EGFR-mAb) with gemcitabine-based chemotherapy as a first-line treatment for locally advanced or metastatic PC. A total of 11 studies were included, with a total sample size of 806 patients with locally advanced or metastatic PC. Meta-analysis results showed that the objective response rate (ORR) for first-line treatment of advanced PC with Anti-EGFR-mAb combined with gemcitabine was 15% (95% CI: 10–22%), and the disease control rate (DCR) was 58% (95% CI: 49–67%). Compared with gemcitabine-based chemotherapy, combination therapy did not improve progression-free time (PFS) (HR = 0.93, 95%CI: 0.81–1.04, <i>p</i> = 0.057) or overall survival (OS) (HR = 0.90, 95%CI: 0.78–1.02, <i>p</i> = 0.04). The incidence of severe adverse events (sAEs) caused by combination therapy was 31% (95% CI: 14–50%). Anti-EGFR-mAb combined with gemcitabine chemotherapy has shown a good efficacy to first-line treatment of advanced PC, it did not provide a significant survival benefit compared to chemotherapy alone. Additionally, combination therapy was associated with a high incidence of AEs, highlighting safety concerns that warrant special attention. PROSPERO (CRD420250652874).