Exposure-response analyses of cabozantinib in patients with metastatic renal cell cancer
| Autor: | Krens, S.D., Erp, N.P. van, Groenland, S.L., Moes, D.J.A.R., Mulder, S.F., Desar, I.M.E., Hulle, T. van der, Steeghs, N., Herpen, C.M.L. van |
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| Rok vydání: | 2022 |
| Předmět: |
Adult
Male Cancer Research Survival Pyridines Antineoplastic Agents Exposure All institutes and research themes of the Radboud University Medical Center Genetics Humans Pharmacokinetics Anilides Carcinoma Renal Cell Aged Retrospective Studies Aged 80 and over Toxicity Dose-Response Relationship Drug Other Research Radboud Institute for Health Sciences [Radboudumc 0] Response Cabozantinib Middle Aged Renal cell carcinoma Kidney Neoplasms Progression-Free Survival Treatment Outcome Pharmacodynamics Oncology Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] Female Drug Monitoring Algorithms Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] |
| Zdroj: | BMC Cancer, 22, 1 BMC Cancer, 22 BMC Cancer, 22(1). BMC |
| ISSN: | 1471-2407 |
| Popis: | AimIn the registration trial, cabozantinib exposure ≥ 750 ng/mL correlated to improved tumor size reduction, response rate and progression free survival (PFS) in patients with metastatic renal cell cancer (mRCC). Because patients in routine care often differ from patients in clinical trials, we explored the cabozantinib exposure–response relationship in patients with mRCC treated in routine care.MethodsCabozantinib trough concentrations (Cmin) were collected and average exposure was calculated per individual. Exposure–response analyses were performed using the earlier identified target of Cmin > 750 ng/mL and median Cmin. In addition, the effect of dose reductions on response was explored. PFS was used as measure of response.ResultsIn total, 59 patients were included:10% were classified as favourable, 61% as intermediate and 29% as poor IMDC risk group, respectively. Median number of prior treatment lines was 2 (0–5). Starting dose was 60 mg in 46%, 40 mg in 42% and 20 mg in 12% of patients. Dose reductions were needed in 58% of patients. Median Cminwas 572 ng/mL (IQR: 496–701). Only 17% of patients had an average Cmin ≥ 750 ng/mL. Median PFS was 52 weeks (95% CI: 40–64). No improved PFS was observed for patients with Cmin ≥ 750 ng/mL or ≥ 572 ng/ml. A longer PFS was observed for patients with a dose reduction vs. those without (65 vs. 31 weeks,p = .001). After incorporating known covariates (IMDC risk group and prior treatment lines (p = .004).ConclusionIn these explorative analyses, no clear relationship between increased cabozantinib exposure and improved PFS was observed. Average cabozantinib exposure was below the previously proposed target in 83% of patients. Future studies should focus on validating the cabozantinib exposure required for long term efficacy. |
| Databáze: | OpenAIRE |
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