Retrospective Comparison of Triple-sequence Therapies in Metastatic Renal Cell Carcinoma.

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 -