Sequence therapy in patients with metastatic renal cell carcinoma
Standard
Sequence therapy in patients with metastatic renal cell carcinoma : comparison of common targeted treatment options following failure of receptor tyrosine kinase inhibitors. / Busch, Jonas; Seidel, Christoph; Kempkensteffen, Carsten; Johannsen, Manfred; Wolff, Ingmar; Hinz, Stefan; Magheli, Ahmed; Miller, Kurt; Grünwald, Viktor; Weikert, Steffen.
in: EUR UROL, Jahrgang 60, Nr. 6, 12.2011, S. 1163-70.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Sequence therapy in patients with metastatic renal cell carcinoma
T2 - comparison of common targeted treatment options following failure of receptor tyrosine kinase inhibitors
AU - Busch, Jonas
AU - Seidel, Christoph
AU - Kempkensteffen, Carsten
AU - Johannsen, Manfred
AU - Wolff, Ingmar
AU - Hinz, Stefan
AU - Magheli, Ahmed
AU - Miller, Kurt
AU - Grünwald, Viktor
AU - Weikert, Steffen
N1 - Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2011/12
Y1 - 2011/12
N2 - BACKGROUND: The best sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been sufficiently defined.OBJECTIVE: To describe the efficacy and toxicity of sequential everolimus (EV) versus receptor tyrosine kinase inhibitor (rTKI) following failure of first rTKI treatment.DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of 108 patients receiving rTKI or EV after progression on rTKI therapy at two German academic centres.INTERVENTION: Sequence of systemic targeted treatment with sunitinib (n=85) or sorafenib (n=23) followed by EV (n=62) or another rTKI (n=46; sorafenib, n=35; sunitinib, n=11).MEASUREMENTS: We measured response rate (Response Evaluation Criteria in Solid Tumours 1.0) and toxicity. Survival analysis (Kaplan-Meier method and Cox regression) was conducted for progression-free survival (PFS) and overall survival (OS).RESULTS AND LIMITATIONS: Main patient characteristics did not significantly differ by sequence of treatment groups (rTKI-rTKI vs rTKI-EV). Response rate following first rTKI failure was not significantly different between sequential therapies with a disease control rate of 51.6% (EV) and 43.5% (rTKI). The corresponding median PFS was 3.6 mo (95% confidence interval [CI], 1.8-5.4) for EV and 4.0 mo (3.2-4.9) for rTKI treatment. The estimated OS was longer for the rTKI-EV group (43 mo; 95% CI, 33.9-52.1) than for the rTKI-rTKI group (29 mo; 95% CI, 18.6-39.5; p=0.03), but this difference lost statistical significance in multivariable-adjusted analyses. Intrinsic rTKI resistance was independently associated with inferior subsequent PFS (hazard ratio [HR]: 1.79; 95% CI, 1.15-3.62; p=0.015) and OS (HR: 6.54; 95% CI, 3.01-14.20; p<0.001). Limitations are the retrospective design, limited numbers of cases, and residual confounding factors.CONCLUSIONS: The sequence therapies rTKI-EV and rTKI-rTKI may be equally efficacious in terms of PFS and response rate, whereas a tendency towards superior survival was observed for the rTKI-EV sequence. These data, particularly the potential benefit of an early change of mode of action, need confirmation in randomised comparative trials.
AB - BACKGROUND: The best sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been sufficiently defined.OBJECTIVE: To describe the efficacy and toxicity of sequential everolimus (EV) versus receptor tyrosine kinase inhibitor (rTKI) following failure of first rTKI treatment.DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of 108 patients receiving rTKI or EV after progression on rTKI therapy at two German academic centres.INTERVENTION: Sequence of systemic targeted treatment with sunitinib (n=85) or sorafenib (n=23) followed by EV (n=62) or another rTKI (n=46; sorafenib, n=35; sunitinib, n=11).MEASUREMENTS: We measured response rate (Response Evaluation Criteria in Solid Tumours 1.0) and toxicity. Survival analysis (Kaplan-Meier method and Cox regression) was conducted for progression-free survival (PFS) and overall survival (OS).RESULTS AND LIMITATIONS: Main patient characteristics did not significantly differ by sequence of treatment groups (rTKI-rTKI vs rTKI-EV). Response rate following first rTKI failure was not significantly different between sequential therapies with a disease control rate of 51.6% (EV) and 43.5% (rTKI). The corresponding median PFS was 3.6 mo (95% confidence interval [CI], 1.8-5.4) for EV and 4.0 mo (3.2-4.9) for rTKI treatment. The estimated OS was longer for the rTKI-EV group (43 mo; 95% CI, 33.9-52.1) than for the rTKI-rTKI group (29 mo; 95% CI, 18.6-39.5; p=0.03), but this difference lost statistical significance in multivariable-adjusted analyses. Intrinsic rTKI resistance was independently associated with inferior subsequent PFS (hazard ratio [HR]: 1.79; 95% CI, 1.15-3.62; p=0.015) and OS (HR: 6.54; 95% CI, 3.01-14.20; p<0.001). Limitations are the retrospective design, limited numbers of cases, and residual confounding factors.CONCLUSIONS: The sequence therapies rTKI-EV and rTKI-rTKI may be equally efficacious in terms of PFS and response rate, whereas a tendency towards superior survival was observed for the rTKI-EV sequence. These data, particularly the potential benefit of an early change of mode of action, need confirmation in randomised comparative trials.
KW - Academic Medical Centers
KW - Aged
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Benzenesulfonates
KW - Carcinoma, Renal Cell
KW - Chi-Square Distribution
KW - Disease-Free Survival
KW - Drug Administration Schedule
KW - Drug Resistance, Neoplasm
KW - Female
KW - Germany
KW - Humans
KW - Indoles
KW - Kaplan-Meier Estimate
KW - Kidney Neoplasms
KW - Male
KW - Middle Aged
KW - Molecular Targeted Therapy
KW - Niacinamide
KW - Phenylurea Compounds
KW - Proportional Hazards Models
KW - Protein Kinase Inhibitors
KW - Pyridines
KW - Pyrroles
KW - Receptor Protein-Tyrosine Kinases
KW - Retrospective Studies
KW - Risk Assessment
KW - Risk Factors
KW - Sirolimus
KW - Survival Rate
KW - Time Factors
KW - Treatment Failure
U2 - 10.1016/j.eururo.2011.07.037
DO - 10.1016/j.eururo.2011.07.037
M3 - SCORING: Journal article
C2 - 21802830
VL - 60
SP - 1163
EP - 1170
JO - EUR UROL
JF - EUR UROL
SN - 0302-2838
IS - 6
ER -