Table 1. Patient characteristics (n = 118).
* Less than 5 each: Rhabdomyosarcoma, angiosarcoma, extraskeletal
myxoid chondrosarcoma, malignant Peripheral Nerve Sheath Tumour,
extraskeletal osteosarcoma, desmoplastic small round cell tumour,
dermatofibrosarcoma
** Grading system does not apply to bone sarcoma, liposarcoma, clear
cell sarcoma, alveolar sarcoma, epithelioid sarcoma, desmoplastic small
round cell tumour<;
n: number
ULN: upper limit of normal
Plasma concentration of pazopanib
Five hundred and twenty-nine samples were assayed with a median of 3
(range 1-20) samples per patient. The target Cmin ≥ 27
mg/L was not reached in 45% of the samples at the first sampling and in
40% in the whole cohort. The initial daily dose of pazopanib was 800
mg/day in 69 patients (58.5%). In this subgroup, the inter-individual
variability in PAZ Cmin was 47.4% at D15. No baseline
characteristic was associated with PAZ Cmin (data not
shown). PAZ Cmin at D15 was significantly higher for
patients treated with 800 mg/day compared with those treated at lower
dosage (34.6 ± 16.4 vs 26.4 ± 11.8 mg/L; p=0.002). Among patients who
received 800 mg/day over the whole sampling period (n = 23), no
variation with time in PAZ Cmin was observed.
Efficacy of pazopanib in STS cohort
Ninety-five STS patients were eligible for the analysis of
survival-exposure relationship.
The median follow-up was 11.4 months (95% CI 1.4-41.1). At data cut-off
in November 2020, 13 STS patients (14%) were still treated with
pazopanib.
The median PFS was 3.30 months (95% CI 2.56-5.06). In univariate
analysis, PAZ Cmin < 27 mg/L at D15 was
associated with a higher risk of progression at 3 months (OR 3.09, 95%
CI [1.31-7.28], p=0.01) unlike to the initial daily dose (table 2).
The multivariate analysis identified PAZ Cmin< 27 mg/L as an independent risk factor of progression (OR
4.21, 95% CI [1.47-12.12], p=0.008), with other bio-clinical
factors (table 2).