Background: Interindividual pharmacokinetic variability may influence the clinical benefit or toxicity of cabozantinib in metastatic renal cell carcinoma (mRCC). We aimed to investigate the exposure-toxicity and exposure-response relationship of cabozantinib in unselected mRCC patients treated in routine care.
Methods: This ambispective multicenter study enrolled consecutive patients receiving cabozantinib in monotherapy. Steady-state trough concentration (Cmin,ss) within the first 3 months after treatment initiation was used for the PK/PD analysis with dose-limiting toxicity (DLT) and survival outcomes. Logistic regression and Cox proportional-hazards models were used to identify the risk factors of DLT and inefficacy in patients, respectively.
Results: Seventy-eight mRCC patients were eligible for the statistical analysis. Fifty-two patients (67%) experienced DLT with a median onset of 2.1 months (95%CI 0.7-8.2). In multivariate analysis, Cmin,ss was identified as an independent risk factor of DLT (OR 1.46, 95%CI [1.04-2.04]; p = 0.029). PFS and OS were not statistically associated with the starting dose (p = 0.81 and p = 0.98, respectively). In the multivariate analysis of PFS, Cmin, ss > 336 ng/mL resulted in a hazard ratio of 0.28 (95%CI, 0.10-0.77, p = 0.014). By contrast, Cmin, ss > 336 ng/mL was not statistically associated with longer OS.
Conclusion: Early plasma drug monitoring may be useful to optimise cabozantinib treatment in mRCC patients treated in monotherapy, especially in frail patients starting at a lower than standard dose.
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http://dx.doi.org/10.1038/s41416-024-02585-y | DOI Listing |
Clin Genitourin Cancer
November 2024
Ankara University School of Medicine, Department of Medical Oncology, Ankara, Turkey; Ankara University Cancer Institute, Ankara, Turkey. Electronic address:
Introduction: Despite the rapid evolution in management of metastatic renal cell carcinoma (mRCC) over the past decade, challenges remain in accessing new therapies in some parts of the world. Despite therapeutic advancements, attrition rates remain persistently high. This study aims to assess the treatment patterns and attrition rates of patients with mRCC in oncology clinics across Turkey.
View Article and Find Full Text PDFJCO Clin Cancer Inform
December 2024
Ontada, Boston, MA.
Purpose: Nivolumab plus ipilimumab (NIVO + IPI) is a first-in-class combination immunotherapy for the treatment of intermediate- or poor (I/P)-risk advanced or metastatic renal cell carcinoma (mRCC). Currently, there are limited real-world data regarding clinical effectiveness beyond 12-24 months from treatment initiation. In this real-world study, treatment patterns and clinical outcomes were evaluated for NIVO + IPI in a community oncology setting.
View Article and Find Full Text PDFClin Exp Metastasis
December 2024
Oncology Unit, Macerata Hospital, Macerata, Italy.
Studies conducted in the last few years have suggested a connection between clinical outcomes and the time of immune checkpoint inhibitors (ICIs) infusion. However, few data are available regarding the differences between early and late time-of-day (ToD) administration in metastatic renal cell carcinoma (mRCC) patients receiving immunotherapy and immune-based combinations. In this meta-analysis, we aimed to fully investigate the influence of timing of administration on the efficacy of mRCC immunotherapy, by comparing early ToD versus late ToD dosing in this setting.
View Article and Find Full Text PDFHeliyon
December 2024
General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Background: Although the lactate pathway has been reported to lead to immune escape through the inhibition of effector T cells, the cancer-intrinsic lactate signature has not been identified, and the immunotherapeutic efficacy and potential mechanism of the lactate signature are still unclear.
Methods: We defined a pan-cancer up-lactate score by comparing malignant tissues and normal tissues in the TCGA cohort. The immunotherapeutic efficacy was evaluated in non-small cell lung cancer (NSCLC), metastatic renal cancer (mRCC), bladder cancer (BLCA) and melanoma cohorts.
Eur Urol Focus
December 2024
Department of Medicine, NYC Health + Hospitals / Jacobi, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address:
Background And Objective: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors (ICIs) is controversial. We aimed to investigate the survival benefit of CN in patients with mRCC treated with ICIs.
Methods: We searched the EMBASE, MEDLINE, and Web of Science databases up to August 26, 2023 to identify studies comparing overall survival (OS) for patients with mRCC treated with ICIs with or without CN.
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