PMID- 34922840
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20230202
IS  - 1938-0682 (Electronic)
IS  - 1558-7673 (Print)
IS  - 1558-7673 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Feb
TI  - Analysis of Toxicity and Clinical Outcomes in Full Versus Reduced Starting Dose 
      Cabozantinib in Metastatic Renal Cell Carcinoma Patients.
PG  - 53-59
LID - S1558-7673(21)00205-6 [pii]
LID - 10.1016/j.clgc.2021.11.004 [doi]
AB  - 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.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Martini, Dylan J
AU  - Martini DJ
AD  - Massachusetts General Hospital, Department of Medicine, Boston, MA; Winship 
      Cancer Institute of Emory University, Atlanta, GA.
FAU - Evans, Sean T
AU  - Evans ST
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Departments of Biostatistics and Bioinformatics, Emory University, Atlanta, GA.
FAU - Shabto, Julie M
AU  - Shabto JM
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Uner, Ogul E
AU  - Uner OE
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Olsen, T Anders
AU  - Olsen TA
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Brown, Jacqueline T
AU  - Brown JT
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Russler, Greta Anne
AU  - Russler GA
AD  - Winship Cancer Institute of Emory University, Atlanta, GA.
FAU - Yantorni, Lauren
AU  - Yantorni L
AD  - Winship Cancer Institute of Emory University, Atlanta, GA.
FAU - Caulfield, Sarah
AU  - Caulfield S
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine, Atlanta, GA; Department of Pharmaceutical Services, Emory University 
      School of Medicine, Atlanta, GA.
FAU - Goldman, Jamie M
AU  - Goldman JM
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Nazha, Bassel
AU  - Nazha B
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Harris, Wayne B
AU  - Harris WB
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Master, Viraj A
AU  - Master VA
AD  - Department of Urology, Emory University School of Medicine, Atlanta, GA.
FAU - Kucuk, Omer
AU  - Kucuk O
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Carthon, Bradley C
AU  - Carthon BC
AD  - Winship Cancer Institute of Emory University, Atlanta, GA; Department of 
      Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, 
      GA.
FAU - Bilen, Mehmet Asim
AU  - Bilen MA
AD  - 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.
LA  - eng
GR  - P30 CA138292/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211112
PL  - United States
TA  - Clin Genitourin Cancer
JT  - Clinical genitourinary cancer
JID - 101260955
RN  - 0 (Anilides)
RN  - 0 (Pyridines)
RN  - 1C39JW444G (cabozantinib)
SB  - IM
MH  - Anilides
MH  - *Carcinoma, Renal Cell/pathology
MH  - Female
MH  - Humans
MH  - *Hypertension
MH  - *Kidney Neoplasms/pathology
MH  - Male
MH  - *Mucositis
MH  - Pyridines
MH  - Retrospective Studies
PMC - PMC8816843
MID - NIHMS1756237
OTO - NOTNLM
OT  - Cabozantinib
OT  - Clinical outcomes
OT  - Dosing
OT  - Metastatic renal cell carcinoma
OT  - Treatment-related adverse events
EDAT- 2021/12/20 06:00
MHDA- 2022/04/30 06:00
PMCR- 2023/02/01
CRDT- 2021/12/19 20:40
PHST- 2021/06/09 00:00 [received]
PHST- 2021/11/01 00:00 [revised]
PHST- 2021/11/07 00:00 [accepted]
PHST- 2021/12/20 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2021/12/19 20:40 [entrez]
PHST- 2023/02/01 00:00 [pmc-release]
AID - S1558-7673(21)00205-6 [pii]
AID - 10.1016/j.clgc.2021.11.004 [doi]
PST - ppublish
SO  - Clin Genitourin Cancer. 2022 Feb;20(1):53-59. doi: 10.1016/j.clgc.2021.11.004. 
      Epub 2021 Nov 12.