Impact of ramucirumab pharmacokinetics in combination with docetaxel on the efficacy and survival in patients with advanced non-small cell lung cancer.
Lung Cancer
; 178: 247-253, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36913912
ABSTRACT
OBJECTIVES:
Ramucirumab, an anti-vascular endothelial growth factor receptor-2 antibody, has been approved for the treatment of non-small cell lung cancer (NSCLC); however, its pharmacokinetic properties in clinical practice are unknown. We aimed to measure ramucirumab concentrations and conduct a retrospective pharmacokinetic analysis using real-world data. MATERIALS ANDMETHODS:
Patients with stage III-IV and recurrent NSCLC who received ramucirumab plus docetaxel were evaluated in this study. After the first administration, the ramucirumab trough concentration (Ctrough) was measured using liquid chromatography-mass spectrometry. Patient characteristics, adverse events, tumor response, and survival time were retrospectively extracted from medical records from August 2, 2016 to July 16, 2021.RESULTS:
A total of 131 patients were examined to assess serum ramucirumab concentrations. Ctrough ranged from below the lower limit of quantification (BLQ) to 48.8 µg/mL (BLQ ≤ 1st quartile (Q1) ≤ 7.34, 7.34 < 2nd quartile (Q2) ≤ 14.7, 14.7 < 3rd quartile (Q3) ≤ 21.9 and 21.9 < 4th quartile (Q4) ≤ 48.8 µg/mL). The overall response rate was significantly higher in Q2-4 than that in Q1 (p = 0.011). The median progression-free survival was marginally longer, and overall survival was significantly longer in Q2-4 (p = 0.009). The Glasgow prognostic score (GPS) in Q1 was significantly higher than in Q2-4 (p = 0.034) and associated with Ctrough (p = 0.002).CONCLUSION:
Patients with higher ramucirumab exposure had a high ORR and prolonged survival time, whereas patients with lower ramucirumab exposure were characterized by a high GPS and poor prognosis. Cachexia may reduce the exposure level of ramucirumab in certain patients, reducing the clinical benefits of ramucirumab treatment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Neoplasias Pulmonares
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Lung Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão