Safety and efficacy profile of pembrolizumab in solid cancer: pooled reanalysis based on randomized controlled trials

Abstract

Background: The aim of the present review is to systematically evaluate the efficacy and safety of pembrolizumab by analyzing survival outcomes and at the same time, to present evidence for future clinical applications of anti-programmed cell death protein 1 (anti-PD-1) antibodies by analyzing the efficacy and safety of pembrolizumab.

Methods: A comprehensive literature search of PubMed, Medline, and Embase was performed for all relevant clinical trials. In this study, adverse events of any grades and grades ≥3 were summarized and calculated for event rates. For controlled trials, odd ratios (ORs) were calculated to determine the role of pembrolizumab in adverse events. The Kaplan-Meier survival curves were extracted for hazard ratio (HR) calculation and survival outcomes were measured by progression-free survival (PFS).

Results: A total of 3,953 patients were included in safety analyses. The results indicated that the overall incidence of any treatment emergent adverse events was 74.3% (95% confidence interval [CI]: 0.671-0.805). The efficacy analysis involving 915 patients with advanced melanoma suggested that 10 mg/kg of pembrolizumab every 3 weeks could improve patients' PFS (HR =0.73, 95% CI: 0.64-0.83).

Conclusion: Pembrolizumab is a promising therapeutic option that could bring better survival outcomes but, at the same time, leads to higher frequency of some adverse events.

Keywords: efficacy; meta-analysis; pembrolizumab; safety.

Figure 1

The flow diagram of the study selection process.

Figure 2

The pooled estimate for overall incidence of any adverse events. Abbreviation: CI, confidence interval.

Figure 3

Forest plot of all-grade adverse events in single-arm trials. Notes: (A) The all-grade adverse event rates and 95% CIs using a fixed-effects model. (B) The all-grade adverse event rates and 95% CIs using a random-effects model. Abbreviation: CI, confidence interval.

Figure 4

Forest plot of grade ≥3 adverse events in single-arm trials. Notes: (A) The grade ≥3 adverse event rates and 95% CIs using a fixed-effects model. (B) The grade ≥3 adverse event rates and 95% CIs using a random-effects model. Abbreviation: CI, confidence interval.

Figure 5

Forest plot of all-grade adverse events in control-arm trials. Notes: (A) The all-grade adverse event rates and 95% CIs using a fixed-effects model. (B) The all-grade adverse event rates and 95% CIs using a random-effects model. Abbreviation: CI, confidence interval.

Figure 6

Forest plot of grade ≥3 adverse events in control-arm trials. Notes: (A) The grade ≥3 adverse event rates and 95% CIs using a fixed-effects model. (B) The grade ≥3 adverse event rates and 95% CIs using a random-effects model. Abbreviation: CI, confidence interval.

Figure 7

The hazard ratios of adverse events in a pembrolizumab treatment group compared to control therapy groups. Abbreviations: CI, confidence interval; SE, standard error.