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

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 178; pp. 247 - 253
• Main 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
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-04-2023
• Subjects: Antibodies, Monoclonal - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cachexia; Carcinoma, Non-Small-Cell Lung - pathology; Docetaxel - therapeutic use; Humans; Liquid chromatography-mass spectrometry; Lung Neoplasms - pathology; Neoplasm Recurrence, Local - drug therapy; Non-small cell lung cancer; Pharmacokinetics; Ramucirumab; Retrospective Studies; CRP; PS; NSCLC; OS; BLQ; VEGF; Liquid chromatography-mass spectrometry; FN; Cachexia; GPS; EGFR; ICI; ORR; DCR; NLR; ECOG; Non-small cell lung cancer; Ramucirumab; PFS; Pharmacokinetics; ADA
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2023.03.001

•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.
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.
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.
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).
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.