Cancer chemotherapy and pharmacology · 2023
Correlation analysis between camrelizumab trough concentration levels and efficacy or safety in East Asian patients with advanced lung cancer.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Cheng Mengfei, Yang Fang, Yang Yanchao, Gao Xinyue, Yu Yang, Wang Nan, Luo Xinyu, Zhang Shuo, Jiang Shuai, Dong Mei
Аннотация
BACKGROUND: Camrelizumab combined with chemotherapy is approved across tumor types. However, only a fraction of patients benefits from immunotherapy, and biomarkers such as the expression of PD-L1, tumor mutational burden, and CXCL11 are expensive and suboptimal specificity for cancer patients. An exposure-response (E-R) relationship has been reported in many immune checkpoint inhibitors (ICIs), and the trough concentrations and other drug exposure metrics are broadly used to guide dosing decisions, assess exposure-outcomes relationships, and ultimately predict outcomes based on those relationships. However, the potential use of trough concentration levels for camrelizumab is still not clear.
METHODS: Blood samples were obtained at trough levels after doses 3 and 4 from 77 patients with advanced lung cancer who received camrelizumab (200 mg Q3 W) monotherapy or combined with chemotherapy. We optimized a competitive ELISA method to measure the trough concentration.
RESULTS: We found that the trough concentration was steady after 3 dose cycles, and the trough concentration level of camrelizumab was higher in patients who developed immune-related adverse effects (irAEs) than in those who did not (P < 0.05) but was not observed in disease progression and PFS (P > 0.05). Age (< 65 years old), no smoking history, and efficacy evaluation after 4-dose treatment were associated with PFS (P < 0.05), but no significance was observed in other clinical characteristics. Total bilirubin and albumin had an influence on trough concentration, and monocytes and albumin were independent risk factors for PFS (P < 0.05).
CONCLUSIONS: Our results suggest that the trough concentration level of camrelizumab might be a risk factor for the occurrence of irAEs in advanced lung cancer, and using the immunotherapy as early as possible may bring better clinical outcomes.
METHODS: Blood samples were obtained at trough levels after doses 3 and 4 from 77 patients with advanced lung cancer who received camrelizumab (200 mg Q3 W) monotherapy or combined with chemotherapy. We optimized a competitive ELISA method to measure the trough concentration.
RESULTS: We found that the trough concentration was steady after 3 dose cycles, and the trough concentration level of camrelizumab was higher in patients who developed immune-related adverse effects (irAEs) than in those who did not (P < 0.05) but was not observed in disease progression and PFS (P > 0.05). Age (< 65 years old), no smoking history, and efficacy evaluation after 4-dose treatment were associated with PFS (P < 0.05), but no significance was observed in other clinical characteristics. Total bilirubin and albumin had an influence on trough concentration, and monocytes and albumin were independent risk factors for PFS (P < 0.05).
CONCLUSIONS: Our results suggest that the trough concentration level of camrelizumab might be a risk factor for the occurrence of irAEs in advanced lung cancer, and using the immunotherapy as early as possible may bring better clinical outcomes.