TY - JOUR
T1 - Evaluating the Clinical Impact and Feasibility of Therapeutic Drug Monitoring of Pazopanib in a Real-World Soft-Tissue Sarcoma Cohort
AU - Meertens, Marinda
AU - Giraud, Eline L.
AU - the Dutch Pharmacology Oncology Group (DPOG)
AU - van der Kleij, Maud B.A.
AU - Westerdijk, Kim
AU - Guchelaar, Niels A.D.
AU - Bleckman, Roos F.
AU - Rieborn, Amy
AU - Imholz, Alex L.T.
AU - Otten, Hans Martin
AU - Vulink, Annelie
AU - Los, Maartje
AU - Hamberg, Paul
AU - van der Graaf, Winette T.A.
AU - Gelderblom, Hans
AU - Moes, Dirk Jan A.R.
AU - Broekman, K. Esther
AU - Touw, Daan J.
AU - Koolen, Stijn L.W.
AU - Mathijssen, Ron H.J.
AU - Huitema, Alwin D.R.
AU - van Erp, Nielka P.
AU - Desar, Ingrid M.E.
AU - Steeghs, Neeltje
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/7/16
Y1 - 2024/7/16
N2 - Introduction and Objective:Pazopanib is registered for metastatic renal cell carcinoma and soft-tissue sarcoma (STS). Its variable pharmacokinetic (PK) characteristics and narrow therapeutic range provide a strong rationale for therapeutic drug monitoring (TDM). Prior studies have defined target levels of drug exposure (≥ 20.5 mg/L) linked to prolonged progression-free survival (PFS), but the added value of using TDM remains unclear. This study investigates the effect of TDM of pazopanib in patients with STS on survival outcomes and dose-limiting toxicities (DLTs) and evaluates the feasibility of TDM-guided dosing. Methods: A TDM-guided cohort was compared to a non-TDM-guided cohort for PFS, overall survival (OS) and DLTs. PK samples were available from all patients, though not acted upon in the non-TDM-guided cohort. We evaluated the feasibility of TDM by comparing the proportion of underdosed patients in our TDM cohort with data from previous publications.Results: A total of 122 STS patients were included in the TDM-guided cohort (n = 95) and non-TDM-guided cohort (n = 27). The average exposure in the overall population was 30.5 mg/L and was similar in both groups. Median PFS and OS did not differ between the TDM-guided cohort and non-TDM-guided cohort (respectively 5.5 vs 4.4 months, p = 0.3, and 12.6 vs 10.1 months, p = 0.8). Slightly more patients in the non-TDM-guided cohort experienced DLTs (54%) compared to the TDM-guided cohort (44%). The proportion of underdosed patients (13.3%) was halved compared to historical data (26.7%). Conclusion: TDM reduced the proportion of patients with subtherapeutic exposure levels by ~ 50%. Nonetheless, the added value of TDM for achieving target trough levels of ≥ 20.5 mg/L for pazopanib on survival outcomes could not be confirmed in STS patients.
AB - Introduction and Objective:Pazopanib is registered for metastatic renal cell carcinoma and soft-tissue sarcoma (STS). Its variable pharmacokinetic (PK) characteristics and narrow therapeutic range provide a strong rationale for therapeutic drug monitoring (TDM). Prior studies have defined target levels of drug exposure (≥ 20.5 mg/L) linked to prolonged progression-free survival (PFS), but the added value of using TDM remains unclear. This study investigates the effect of TDM of pazopanib in patients with STS on survival outcomes and dose-limiting toxicities (DLTs) and evaluates the feasibility of TDM-guided dosing. Methods: A TDM-guided cohort was compared to a non-TDM-guided cohort for PFS, overall survival (OS) and DLTs. PK samples were available from all patients, though not acted upon in the non-TDM-guided cohort. We evaluated the feasibility of TDM by comparing the proportion of underdosed patients in our TDM cohort with data from previous publications.Results: A total of 122 STS patients were included in the TDM-guided cohort (n = 95) and non-TDM-guided cohort (n = 27). The average exposure in the overall population was 30.5 mg/L and was similar in both groups. Median PFS and OS did not differ between the TDM-guided cohort and non-TDM-guided cohort (respectively 5.5 vs 4.4 months, p = 0.3, and 12.6 vs 10.1 months, p = 0.8). Slightly more patients in the non-TDM-guided cohort experienced DLTs (54%) compared to the TDM-guided cohort (44%). The proportion of underdosed patients (13.3%) was halved compared to historical data (26.7%). Conclusion: TDM reduced the proportion of patients with subtherapeutic exposure levels by ~ 50%. Nonetheless, the added value of TDM for achieving target trough levels of ≥ 20.5 mg/L for pazopanib on survival outcomes could not be confirmed in STS patients.
UR - https://www.scopus.com/pages/publications/85198957952
U2 - 10.1007/s40262-024-01399-8
DO - 10.1007/s40262-024-01399-8
M3 - Article
C2 - 39012619
AN - SCOPUS:85198957952
SN - 0312-5963
VL - 63
SP - 1045
EP - 1054
JO - Clinical Pharmacokinetics
JF - Clinical Pharmacokinetics
IS - 7
ER -