Tailoring oral targeted therapies dosage in lung cancer: A systematic review of pharmacokinetics studies on renal and hepatic impairment

Abstract

Background: Lung cancer is the leading cause of cancer-related deaths worldwide, and stage IV lung cancer is frequently managed with targeted therapy. Renal and hepatic impairment frequently coexist with cancer, often requiring a reduction in targeted therapy dosage. This systematic review assesses the appropriateness of current targeted therapy dosage adjustments in individuals with hepatic and renal impairment by comparing package insert recommendations with available pharmacokinetic studies.

Methods: We reviewed the most recent guidelines from the National Comprehensive Cancer Network (NCCN) on the use of non-monoclonal antibody targeted therapy. We also examined all package inserts for information on dose adjustment in cases of hepatic and renal impairment. We then systematically searched for studies that involved pharmacokinetic analysis in populations with hepatic or renal impairment, as well as those undergoing hemodialysis and peritoneal dialysis.

Results: We identified 44 studies from 21 oral lung cancer therapies that met the inclusion criteria. We developed 13 new recommendations and updated 7 existing ones regarding targeted therapy dose adjustment in cases of hepatic and renal impairment compared to the information provided in the package insert. Several drugs have not published their pharmacokinetic results in a scientific journal, which limits access to their appropriateness. Moreover, there is a lack of research on pharmacokinetic analysis of targeted therapy in patients undergoing hemodialysis and peritoneal dialysis.

Conclusions: Adjusting the dosage of targeted therapy in hepatic and renal impairment based on pharmacokinetic analysis is essential to broaden the usage, improve effectiveness, and minimize side effects. Further pharmacokinetic research on the usage in unstudied populations is strongly advised.

Prospero registration number: CRD42024518123.

Fig 1. Graphical visualization of the research methodology.

NCCN = National Comprehensive Cancer Network; SCLC = small cell lung cancer; NSCLC = non-small cell lung cancer; AUC_0-∞ = area under the concentration from time 0 extrapolated to infinity; C_max= maximum serum concentration; PopPK = population pharmacokinetic; PBPK = physiologically based pharmacokinetic; PROBAST = Prediction model risk of bias assessment tool; NOS = Newcastle–Ottawa Scale; RoB = risk of bias.

Fig 2. PRISMA flowchart.

Fig 3. Summary of findings on dosage of oral targeted therapies for lung cancer in hepatic and renal impairment.

Green box indicates that no adjustment is needed in cases of hepatic or liver impairment. Yellow box indicates the absence of a pharmacokinetic study in individuals with severe hepatic or liver impairment, indicating the need of close monitoring. Red box indicates that oral targeted therapy dosage should be reduced based on either the Child-Pugh score or the estimated glomerular filtration rate.