Analysis of Toxicity and Clinical Outcomes in Full Versus Reduced Starting Dose Cabozantinib in Metastatic Renal Cell Carcinoma Patients.

Autor: Martini DJ; Massachusetts General Hospital, Department of Medicine, Boston, MA; Winship Cancer Institute of Emory University, Atlanta, GA., Evans ST; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Liu Y; Departments of Biostatistics and Bioinformatics, Emory University, Atlanta, GA., Shabto JM; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Uner OE; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Olsen TA; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Brown JT; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Russler GA; Winship Cancer Institute of Emory University, Atlanta, GA., Yantorni L; Winship Cancer Institute of Emory University, Atlanta, GA., Caulfield S; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA; Department of Pharmaceutical Services, Emory University School of Medicine, Atlanta, GA., Goldman JM; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Nazha B; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Harris WB; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Master VA; Department of Urology, Emory University School of Medicine, Atlanta, GA., Kucuk O; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Carthon BC; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA., Bilen MA; Winship Cancer Institute of Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA. Electronic address: mehmet.a.bilen@emory.edu.
Jazyk: angličtina
Zdroj: Clinical genitourinary cancer [Clin Genitourin Cancer] 2022 Feb; Vol. 20 (1), pp. 53-59. Date of Electronic Publication: 2021 Nov 12.
DOI: 10.1016/j.clgc.2021.11.004
Abstrakt: Background: Full dose cabozantinib for metastatic renal cell carcinoma (mRCC) is 60 mg, but adverse events (AEs) may require dose reductions. Limited data exist comparing efficacy among cabozantinib doses. We compared AEs and clinical outcomes in mRCC patients treated with full vs. reduced starting cabozantinib dose.
Methods: We performed a retrospective analysis of 87 mRCC patients treated with cabozantinib at Winship Cancer Institute from 2016 to 2019. Overall survival (OS), progression-free survival (PFS), and objective response (OR) rate measured clinical outcomes. AEs were collected from clinic notes and the most common were hypertension, mucositis/hand-foot skin reaction (HFSR), or gastrointestinal toxicity. Univariate analysis (UVA) between starting doses and AEs with clinical outcomes was performed using logistic regression model. Multivariable analysis was also performed using Cox proportional hazard model.
Results: Most patients were men (71%) with clear-cell RCC (72%). The majority were IMDC intermediate (58%) or poor (35%) risk. One third received first-line cabozantinib and 64% had ≥3 baseline metastatic sites. Most patients (68%) required dose reduction from 60 mg or started at reduced dose without escalation. Reduced dose patients were more likely to have ≥3 distant metastatic sites (70% vs. 58%) and ≥2 prior lines of systemic therapy (50% vs. 40%) compared to full dose patients. UVA revealed a trend towards shorter OS (HR: 1.78, P = .095), PFS (HR: 1.50, P = .107), and lower chance of OR (HR:0.42, P = .149) among reduced dose patients. This trend did not hold in Multivariable analysis (OS HR: 1.20, P = .636; PFS HR: 1.23, P = .4662). Mucositis/HFSR and hypertension were significantly associated with improved outcomes in UVA.
Conclusions: Although we found a trend favoring full dose cabozantinib, this is likely due to worse baseline disease characteristics among patients starting on a reduced dose. Hypertension and mucositis/HFSR may be associated with improved outcomes. Larger studies are warranted to validate these findings.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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