RESUMO
This systematic review and meta-analysis aimed to verify the association between the genetic variants of adenosine triphosphate (ATP)-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) genes and the presence and severity of gefitinib-associated adverse reactions. We systematically searched PubMed, Virtual Health Library/Bireme, Scopus, Embase, and Web of Science databases for relevant studies published up to February 2024. In total, five studies were included in the review. Additionally, eight genetic variants related to ABCB1 (rs1045642, rs1128503, rs2032582, and rs1025836) and ABCG2 (rs2231142, rs2231137, rs2622604, and 15622C>T) genes were analyzed. Meta-analysis showed a significant association between the ABCB1 gene rs1045642 TT genotype and presence of diarrhea (OR = 5.41, 95% CI: 1.38-21.14, I2 = 0%), the ABCB1 gene rs1128503 TT genotype and CT + TT group and the presence of skin rash (OR = 4.37, 95% CI: 1.51-12.61, I2 = 0% and OR = 6.99, 95%CI: 1.61-30.30, I2= 0%, respectively), and the ABCG2 gene rs2231142 CC genotype and presence of diarrhea (OR = 3.87, 95% CI: 1.53-9.84, I2 = 39%). No ABCB1 or ABCG2 genes were positively associated with the severity of adverse reactions associated with gefitinib. In conclusion, this study showed that ABCB1 and ABCG2 variants are likely to exhibit clinical implications in predicting the presence of adverse reactions to gefitinib.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Gefitinibe , Proteínas de Neoplasias , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Gefitinibe/efeitos adversos , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , GenótipoRESUMO
This study aimed to perform a metaanalysis comparing the efficacy and safety of gefitinib in combination with chemotherapy versus gefitinib alone in patients with advanced NonSmall Cell Lung Cancer (NSCLC). We searched databases for clinical studies that reported the efficacy or safety of gefitinib plus chemotherapy in comparison with gefitinib alone. Raw data from included studies were extracted and pooled to calculate the Odds Ratio (OR) for Objective Response Rate (ORR) and Disease Control Rate (DCR), the Hazard Ratio (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), and OR for complication ≥ Grade 3. A total of 10 studies containing 1,528 patients with NSCLC were identified and included in the analysis. Gefitinib plus chemotherapy showed significantly better efficacy in improving ORR (OR = 1.54; 95% CI [Confidence Interval], 1.13â2.1; p = 0.006), DCR (OR = 1.62; 95% CI 1.14â2.29; p = 0.007), PFS (HR=1.67; 95% CI 1.45â1.94; p < 0.001) and OS (HR = 1.49; 95% CI 1.2â1.87; p < 0.001) as compared with gefitinib alone. Consistent results were observed in the sub-population with positive EGFR mutation. The combination of gefitinib with chemotherapy had a significantly higher risk of complication (≥ Grade 3) with an OR of 3.29 (95% CI 2.57â4.21; p < 0.001). The findings in the present study suggest that the combination of gefitinib with chemotherapy can provide better disease response and survival outcomes for patients with advanced NSCLC.