Banca de DEFESA: DARY MEDEIROS DANTAS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : DARY MEDEIROS DANTAS
DATE: 20/03/2026
TIME: 10:30
LOCAL: Sala de Aulas GEP/MEJC
TITLE:

EFFICACY AND SAFETY OF PEMBROLIZUMAB IN ADVANCED CERVICAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS

KEY WORDS:

Pembrolizumab; Cervical Cancer; Immunotherapy; Meta- analysis; Randomized Controlled Trials; Immune Checkpoint. 

PAGES: 25
BIG AREA: Ciências da Saúde
AREA: Saúde Coletiva
SUMMARY:

Programmed cell death protein-1 (PD-1) inhibitors have been extensively investigated and established as a promising therapeutic strategy in the treatment of cervical cancer (CC), particularly as immune checkpoint inhibitors capable of restoring endogenous anti-tumor immunity. Pembrolizumab, a humanized monoclonal antibody that acts as an immune checkpoint inhibitor, received accelerated FDA approval in 2018 and subsequent expanded approvals for the treatment of recurrent or metastatic CC with positive PD-L1 expression. Phase III clinical trials have demonstrated substantial and clinically significant improvement in overall survival (OS) when pembrolizumab is combined with chemotherapy, with or without bevacizumab. The aim of this systematic review was to comprehensively evaluate the efficacy, safety, and certainty of evidence for pembrolizumab, alone or in combination with bevacizumab and chemotherapy, in the treatment of advanced, recurrent, or metastatic cervical cancer, with detailed subgroup analyses according to PD-L1 expression and concomitant bevacizumab use. A systematic review and meta-analysis of phase III randomized controlled trials (RCTs) was conducted in strict accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with prospective registration in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024531233). Phase III RCTs comparing pembrolizumab-based regimens versus standard care/placebo were included. The databases searched were PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library (up to July 2025). The primary outcomes were overall survival (OS) and progression-free survival (PFS), expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes included objective response rate (ORR), complete response (CR), partial response (PR), and adverse events (AEs) of any grade and grade ≥3. Certainty of evidence was systematically assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Four RCTs (n = 2,911 participants), including the paradigmatic KEYNOTE-826 and KEYNOTE-A18 trials, were analyzed. Pembrolizumab significantly improved OS (HR 0.66; 95% CI 0.59–0.73; I² = 12%; high certainty of evidence) and PFS (HR 0.65; 95% CI 0.59–0.71; I² = 8%; high certainty). Benefits were consistent and of clinically relevant magnitude across subgroups with PD-L1 combined positive score (CPS) ≥1 (subgroup HR 0.63) and ≥10 (subgroup HR 0.58), demonstrating benefit independent of PD- L1 expression level or concomitant bevacizumab use. Clinically significant increases in ORR (OR 1.74; 95% CI 1.47–2.05) and complete response rates (OR 1.61; 95% CI 1.27–2.05) were observed. The incidence of grade ≥3 adverse events was moderately elevated in the pembrolizumab group (79.1% vs. 72.7%; OR 1.42), predominantly hematologic toxicities, with a safety profile considered clinically manageable in the context of survival benefit. Pembrolizumab-based therapeutic regimens substantially and significantly improve overall survival and treatment response in advanced cervical cancer, with high- certainty evidence, establishing them as first-line standard of care in accordance with recent FDA approvals. These robust findings strongly support the integration of pembrolizumab into multidisciplinary treatment protocols, particularly for patients with PD-L1-positive cervical cancer, representing a significant milestone in the evolution of gynecologic oncology treatment.

COMMITTEE MEMBERS:
Externa ao Programa - 2323511 - ADRIANA AUGUSTO DE REZENDE - nullExterno à Instituição - IRAMI ARAUJO FILHO - UnP
Presidente - ***.283.220-** - RICARDO NEY OLIVEIRA COBUCCI - UFRN