Meta-analysis of phase III randomized trials of molecular targeted therapies for advanced pancreatic cancer
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Published on: July 25, 2020
Karim M Eltawil1, Paul D Renfrew, Michele Molinari
1Department of Surgery, Queen Elizabeth II Health Sciences Center, Dalhousie University, Halifax, NS, Canada.
Objectives:
For patients with unresectable pancreatic cancer (PC), the efficacy and safety of molecular targeted agents (MTAs) in combination with gemcitabine are still unclear. Published randomized controlled trials (RCTs) have reported conflicting results. This study aimed to conduct a systematic review of the literature and to perform a meta-analysis if appropriate.
Methods:
Seven electronic databases were searched using a standard technique to November 2011 without restriction on publication status or language. The primary aim was to assess overall survival (OS). Secondary aims were to assess progression-free survival (PFS), overall response rates (ORRs) and grade 3, 4 and 5 toxicities. A random-effects model was used for the meta-analysis.
Results:
Seven Phase III RCTs were identified; 1981 patients were treated with MTAs and gemcitabine, and 1992 patients received gemcitabine with or without placebo. No statistically significant difference in OS was found between the two groups [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.85-1.02; P = 0.13]. The addition of MTAs improved PFS (HR = 0.86, 95% CI 0.79-0.93; P = 0.000) and ORR (odds ratio 1.35, 95% CI 1.05-1.74; P = 0.01). However, these benefits were accompanied by significantly higher toxicity (P = 0.001).
Conclusions:
The findings of this study suggest that the palliation of PC with gemcitabine and MTAs does not provide a significant survival benefit and is associated with increased grade 3 and 4 toxicities.
Insights
Adding molecular targeted agents (MTAs) to gemcitabine for pancreatic cancer (PC) did not improve overall survival. This combination therapy increased progression-free survival and response rates but also led to significantly higher toxicities.
Area of Science:
- Oncology
- Clinical Trials
- Pharmacology
Background:
- Unresectable pancreatic cancer (PC) remains a challenging diagnosis with limited treatment options.
- The efficacy and safety of combining molecular targeted agents (MTAs) with gemcitabine for PC are not well-established.
- Previous randomized controlled trials (RCTs) have yielded conflicting results regarding this combination therapy.
Purpose of the Study:
- To systematically review and meta-analyze published RCTs evaluating MTAs combined with gemcitabine for unresectable PC.
- To assess the impact of this combination on overall survival (OS), progression-free survival (PFS), and overall response rates (ORR).
- To evaluate the safety profile, specifically grade 3, 4, and 5 toxicities, associated with MTA and gemcitabine combination therapy.
Main Methods:
- A comprehensive literature search of seven electronic databases was conducted up to November 2011.
- Seven Phase III RCTs involving 1981 patients treated with MTAs and gemcitabine and 1992 patients treated with gemcitabine (with or without placebo) were included.
- A random-effects model was employed for the meta-analysis to determine hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CI).
Main Results:
- No statistically significant difference in overall survival (OS) was observed between the combination therapy and gemcitabine alone (HR = 0.93, P = 0.13).
- The addition of MTAs significantly improved progression-free survival (PFS) (HR = 0.86, P = 0.000) and overall response rates (ORR) (OR = 1.35, P = 0.01).
- However, the combination therapy was associated with a significant increase in grade 3, 4, and 5 toxicities (P = 0.001).
Conclusions:
- The combination of gemcitabine with MTAs for unresectable pancreatic cancer does not offer a significant survival benefit.
- While the combination improves PFS and ORR, it is accompanied by a substantial increase in severe toxicities.
- These findings suggest that the current benefits of MTA and gemcitabine combination therapy in PC palliation are outweighed by increased toxicity without a survival advantage.
