Hepatotoxicity and efficacy associated with first- and new-generation EGFR-TKIs in patients with NSCLC: a systematic review and meta-analysis

Resumo original em inglês

O que aconteceu

While hepatotoxicity has been widely reported with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), the comparative risk among them remains unclear. This study aimed to directly compare the relative risk (RR) of hepatotoxicity between new-generation (afatinib, osimertinib, dacomitinib) and first-generation (gefitinib, erlotinib) EGFR-TKIs in non-small-cell lung cancer (NSCLC) and to evaluate their overall risk-benefit profile.

PubMed, Embase, Cochrane library databases and clinicaltrials.gov were searched for trials up to September 2025. A study protocol was registered in PROSPERO: CRD42023457906. Among the 5371 records identified, 6 studies finally fulfilled the established criteria. Data extracted for each study included study characteristics, baseline patient information, interventions and data on all-grades alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) elevation, overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). RR, hazard ratio (HR) and 95% confidence interval (CI) were calculated using the inverse variance method.

O que encontraram

Six trials involving 2528 patients were analyzed. Decreased risks of hepatotoxicity due to the elevation of AST and ALT were observed for each new-generation EGFR-TKI. The pooled RRs of all-grades ALT, AST and TB elevation were 0.36 (95% CI 0.24-0.52, P < 0.001), 0.44 (95% CI 0.36-0.54, P < 0.001) and 0.83 (95% CI 0.50-1.39, P = 0.48), respectively. New-generation TKIs did achieved benefit in PFS (HR 0.65, 95% CI 0.50-0.83, P < 0.0001) and ORR (RR 1.14, 95% CI 1.00-1.29, P = 0.04). The OS of patients with new-generation TKI treatment was extended (afatinib, HR 0.73, 95% CI 0.58-0.92, P = 0.008 and osimertinib, HR 0.71, 95% CI 0.53-0.95, P = 0.02), except dacomitinib (HR 0.97, 95% CI 0.72-1.29, P = 0.81).

Por que isso importa

New-generation EGFR-TKIs (afatinib, osimertinib, and dacomitinib) demonstrate a superior efficacy and safety profile, with a significantly lower risk of hepatotoxicity, compared to gefitinib and erlotinib.

Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.