Impact of ramucirumab pharmacokinetics in combination with docetaxel on the efficacy and survival in patients with advanced non-small cell lung cancer
Menée dans un contexte de vie réelle à partir de données portant sur 131 patients atteints d'un cancer du poumon non à petites cellules de stade avancé, cette étude rétrospective analyse les caractéristiques pharmacocinétiques du ramucirumab en combinaison avec le docétaxel puis évalue sa toxicité et son efficacité du point de vue du taux de réponse globale, de la survie sans progression et de la survie globale
Résumé en anglais
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 and Methods: 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.
