Impact of ramucirumab pharmacokinetics in combination with docetaxel on the efficacy and survival in patients with advanced non-small cell lung cancer. (April 2023)

• Record Type: Journal Article
• Authors: Akagi, Kazumasa; Yagishita, Shigehiro; Ohuchi, Mayu; Hayashi, Yoshiharu; Takeyasu, Yuki; Masuda, Ken; Shinno, Yuki; Okuma, Yusuke; Yoshida, Tatsuya; Goto, Yasushi; Horinouchi, Hidehito; Yamamoto, Noboru; Mukae, Hiroshi; Ohe, Yuichiro; Hamada, Akinobu
• Is Part Of: Lung cancer. Volume 178(2023)
• Page Start: 247
• Page End: 253
• Publication Date: 2023-04
• Subjects: ADA Anti-drug antibodies -- BLQ Below the lower limit of quantification -- CRP C-reactive protein -- DCR Disease control rate -- ECOG Eastern Cooperative Oncology Group -- EGFR Epidermal growth factor receptor -- FN Febrile neutropenia -- GPS Glasgow prognostic score -- ICI Immune checkpoint inhibitors -- NLR Neutrophil-to-lymphocyte ratios -- NSCLC Non-small cell lung cancer -- ORR Overall response rate -- OS Overall survival -- PFS Progression-free survival -- PS Performance status -- VEGF Vascular endothelial growth factor; Cachexia -- Liquid chromatography-mass spectrometry -- Non-small cell lung cancer -- Pharmacokinetics -- Ramucirumab; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2023.03.001
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: We developed a novel method to analyze ramucirumab concentration using LC-MS/MS. The high concentration group had a high overall response rate and long survival time. The low concentration group was characterized by hypoalbuminemia and high CRP levels. Cachexia may reduce ramucirumab concentration due to hypercatabolism. 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 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.