Retrospective Comparison of Triple-sequence Therapies in Metastatic Renal Cell Carcinoma.
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Retrospective Comparison of Triple-sequence Therapies in Metastatic Renal Cell Carcinoma. / Busch, Jonas; Seidel, Christoph; Erber, Barbara; Issever, Ahi Sema; Hinz, Stefan; Kempkensteffen, Carsten; Magheli, Ahmed; Miller, Kurt; Grünwald, Viktor; Weikert, Steffen.
in: EUR UROL, Jahrgang 64, Nr. 1, 1, 2013, S. 62-70.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Retrospective Comparison of Triple-sequence Therapies in Metastatic Renal Cell Carcinoma.
AU - Busch, Jonas
AU - Seidel, Christoph
AU - Erber, Barbara
AU - Issever, Ahi Sema
AU - Hinz, Stefan
AU - Kempkensteffen, Carsten
AU - Magheli, Ahmed
AU - Miller, Kurt
AU - Grünwald, Viktor
AU - Weikert, Steffen
N1 - Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2013
Y1 - 2013
N2 - BACKGROUND: The optimal sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been defined.OBJECTIVE: To describe the efficacy and toxicity of the most common sequences of targeted therapy, namely, receptor tyrosine kinase inhibitor (rTKI) and mammalian target of rapamycin inhibitor (mTORi), in different sequences after failure of vascular endothelial growth factor signaling inhibition (VEGFi) in first-line therapy.DESIGN, SETTING AND PARTICIPANTS: Retrospective study of 103 patients receiving VEGFi-rTKI-mTORi (n=62) or VEGFi-mTORi-rTKI (n=41) at two German academic centers.INTERVENTION: Sequence of systemic targeted treatment.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Response was assessed using Response Evaluation Criteria in Solid Tumors 1.0 and toxicity was measured using the Common Terminology Criteria for Adverse Events 3.0. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors of survival were analyzed using Cox regression.RESULTS AND LIMITATIONS: Sequence groups did not significantly differ by patient characteristics and response rate following first VEGFi failure. Median PFS for second-line therapy was 4.6 mo (95% confidence interval [CI], 3.8-5.4), 4.1 mo (95% CI, 3.4-4.9) for rTKI treatment, and 5.4 mo (95% CI, 2.7-8.1) for mTORi treatment (p=0.400). No differences in PFS were observed among third-line therapy groups (3.6 mo for mTORi; 3.7 mo for rTKI). Treatment duration following first VEGFi failure (combined second- and third-line PFS) was 10.0 mo for VEGFi-rTKI-mTORi and 12.2 mo for VEGFi-mTORi-rTKI (p=0.103). No significant differences in OS were observed among sequence groups (33.7 mo [95% CI, 30.4-37.1] for VEGFi-rTKI-mTORi; 38.7 mo [95% CI, 24.4-52.9] for VEGFi-mTORi-rTKI). Primary resistance on first-line therapy was an independent predictor of OS, but type of sequence was not. Limitations are the retrospective design and limited numbers of cases.CONCLUSIONS: The sequence therapies VEGFi-mTORi-rTKI and VEGFi-rTKI-mTORi with the currently available agents appear to be equally efficacious in terms of PFS, OS, and response rate, with no apparent beneficial effect with an early use of mTORi.
AB - BACKGROUND: The optimal sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been defined.OBJECTIVE: To describe the efficacy and toxicity of the most common sequences of targeted therapy, namely, receptor tyrosine kinase inhibitor (rTKI) and mammalian target of rapamycin inhibitor (mTORi), in different sequences after failure of vascular endothelial growth factor signaling inhibition (VEGFi) in first-line therapy.DESIGN, SETTING AND PARTICIPANTS: Retrospective study of 103 patients receiving VEGFi-rTKI-mTORi (n=62) or VEGFi-mTORi-rTKI (n=41) at two German academic centers.INTERVENTION: Sequence of systemic targeted treatment.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Response was assessed using Response Evaluation Criteria in Solid Tumors 1.0 and toxicity was measured using the Common Terminology Criteria for Adverse Events 3.0. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors of survival were analyzed using Cox regression.RESULTS AND LIMITATIONS: Sequence groups did not significantly differ by patient characteristics and response rate following first VEGFi failure. Median PFS for second-line therapy was 4.6 mo (95% confidence interval [CI], 3.8-5.4), 4.1 mo (95% CI, 3.4-4.9) for rTKI treatment, and 5.4 mo (95% CI, 2.7-8.1) for mTORi treatment (p=0.400). No differences in PFS were observed among third-line therapy groups (3.6 mo for mTORi; 3.7 mo for rTKI). Treatment duration following first VEGFi failure (combined second- and third-line PFS) was 10.0 mo for VEGFi-rTKI-mTORi and 12.2 mo for VEGFi-mTORi-rTKI (p=0.103). No significant differences in OS were observed among sequence groups (33.7 mo [95% CI, 30.4-37.1] for VEGFi-rTKI-mTORi; 38.7 mo [95% CI, 24.4-52.9] for VEGFi-mTORi-rTKI). Primary resistance on first-line therapy was an independent predictor of OS, but type of sequence was not. Limitations are the retrospective design and limited numbers of cases.CONCLUSIONS: The sequence therapies VEGFi-mTORi-rTKI and VEGFi-rTKI-mTORi with the currently available agents appear to be equally efficacious in terms of PFS, OS, and response rate, with no apparent beneficial effect with an early use of mTORi.
KW - Academic Medical Centers
KW - Aged
KW - Angiogenesis Inhibitors
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Carcinoma, Renal Cell
KW - Disease-Free Survival
KW - Female
KW - Germany
KW - Humans
KW - Kaplan-Meier Estimate
KW - Kidney Neoplasms
KW - Male
KW - Middle Aged
KW - Molecular Targeted Therapy
KW - Multivariate Analysis
KW - Proportional Hazards Models
KW - Protein Kinase Inhibitors
KW - Receptors, Vascular Endothelial Growth Factor
KW - Retrospective Studies
KW - Risk Factors
KW - TOR Serine-Threonine Kinases
KW - Time Factors
KW - Treatment Failure
U2 - 10.1016/j.eururo.2012.09.004
DO - 10.1016/j.eururo.2012.09.004
M3 - SCORING: Journal article
C2 - 22999519
VL - 64
SP - 62
EP - 70
JO - EUR UROL
JF - EUR UROL
SN - 0302-2838
IS - 1
M1 - 1
ER -