Real-world pharmacokinetics of ramucirumab in combination with erlotinib and docetaxel for advanced non-small cell lung cancer: a prospective cohort study

Purpose In pivotal phase III studies of non-small cell lung cancer (NSCLC), ramucirumab (RAM) serum concentrations were associated with clinical outcomes in docetaxel (DTX) plus RAM treatment (DTX group), but not in erlotinib (ERL) plus RAM treatment (ERL group). This study prospectively examined the relationship between serum RAM concentrations and clinical outcomes in a real-world setting. Methods This study included patients with advanced NSCLC who received RAM in combination with DTX or ERL. Blood samples were obtained at trough levels before RAM administration. The day 1 sample of the second cycle was defined as C _trough and measured using liquid chromatography–tandem mass spectrometry. The associations between C _trough and clinical outcomes were evaluated. Results C _trough ranged from 4.3–36.4 µg/mL in the DTX group and 10.2–44.5 µg/mL in the ERL group. Edema was more commonly observed in the high C _trough group than in the DTX group. C _trough was not associated with prognosis in the DTX group, while the median progression-free survival (PFS) was significantly longer in high C _trough (8.3 vs 16.4 months, p  = 0.032) within the ERL group. The median overall survival was significantly longer in low modified Glasgow Prognostic Score (mGPS-low) (32.8 vs 13.6 months, p  = 0.042) within the DTX group, and PFS was significantly longer in mGPS-low (18.2 vs 6.1 months, p  = 0.004) within the ERL group. Conclusion RAM C _trough may influence survival after ERL + RAM treatment. The mGPS appears to be a potential prognostic factor in patients with NSCLC treated with RAM.