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Landscape targeted of therapy in advanced pancreatic adenocarcinoma: a network meta-analysis of randomized controlled
Huixin Ma1, Sheng Wang1, Yunjin Ya2
1The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
Background:
Advanced pancreatic adenocarcinoma (PA) remains a formidable challenge with limited therapeutic options. Gemcitabine-based regimens, often combined with novel targeted therapies, are widely employed, yet their comparative efficacy is poorly understood. This network meta-analysis (NMA) aimed to systematically evaluate the efficacy of various targeted drug combinations in previously treated patients with advanced or metastatic PA.
Methods:
A systematic search of PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov was conducted to retrieve relevant randomized controlled trials (RCTs) published between 2010 and 2024. Studies comparing targeted drug combinations with chemotherapy or chemotherapy alone in advanced/metastatic PA were included in the NMA. The primary outcomes of the study were overall survival (OS) and progression-free survival (PFS), which were assessed using hazard ratios (HRs) with 95% confidence intervals (CIs) and presented in a Forest plot. Surface under the cumulative ranking (SUCRA) scores were calculated to rank treatment efficacy.
Results:
In total, 13 RCTs, comprising 4,665 patients and evaluating 13 targeted drug combinations, were included in the NMA. While no statistically significant improvements in OS or PFS were observed for most targeted drug combinations compared with gemcitabine monotherapy, epidermal growth factor receptor (EGFR)-targeted agents, particularly nimotuzumab, demonstrated a significant survival benefit in specific subgroups. Similarly, indirect comparisons among targeted therapies revealed no significant differences. The SUCRA rankings identified gemcitabine plus nimotuzumab (Gem-Nimot; 98%) as having the highest probability of ranking first for OS, followed by gemcitabine plus masitinib (Gem-Masit; 80%), gemcitabine plus erlotinib (Gem-Erlot; 70%), and gemcitabine plus sorafenib (Gem-Soraf; 23%). For PFS, Gem-Nimot (98%) ranked highest, followed by Gem-Erlot (73%), gemcitabine plus rigosertib (Gem-Rigos; 57%), and gemcitabine plus sunitinib (Gem-Sunit; 8%).
Conclusions:
This NMA combining network and forest plot results showed that Gem-Nimot provided significant survival benefits in advanced PA. EGFR-targeted combinations demonstrated a significant advantage in both OS and PFS compared with gemcitabine alone, indicating that EGFR inhibition may provide real clinical benefits.
Insights
Gemcitabine plus nimotuzumab significantly improves survival in advanced pancreatic cancer. Epidermal growth factor receptor (EGFR)-targeted therapies offer benefits over gemcitabine alone, highlighting EGFR inhibition
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Advanced pancreatic adenocarcinoma (PA) presents a significant therapeutic challenge.
- Current treatments, including gemcitabine-based regimens and targeted therapies, lack comparative efficacy data.
- Understanding the efficacy of targeted drug combinations is crucial for previously treated patients.
Purpose of the Study:
- To systematically evaluate the efficacy of various targeted drug combinations in advanced or metastatic pancreatic cancer.
- To compare the effectiveness of different targeted therapies against gemcitabine monotherapy.
- To identify optimal treatment strategies for previously treated patients with advanced PA.
Main Methods:
- A network meta-analysis (NMA) of randomized controlled trials (RCTs) published between 2010 and 2024.
- Systematic literature search across major databases (PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov).
- Assessment of overall survival (OS) and progression-free survival (PFS) using hazard ratios (HRs) and Surface Under the Cumulative Ranking (SUCRA) scores.
Main Results:
- 13 RCTs with 4,665 patients evaluated 13 targeted drug combinations.
- Gemcitabine plus nimotuzumab (Gem-Nimot) showed the highest probability for improved OS (98%) and PFS (98%).
- Epidermal growth factor receptor (EGFR)-targeted agents, particularly nimotuzumab, demonstrated significant survival benefits in specific subgroups.
Conclusions:
- Gemcitabine plus nimotuzumab (Gem-Nimot) provides significant survival benefits in advanced pancreatic cancer.
- EGFR-targeted combinations show a significant advantage in OS and PFS compared to gemcitabine alone.
- EGFR inhibition represents a promising therapeutic strategy for advanced PA.
