Alternating Treatment With Pazopanib and Everolimus vs Continuous Pazopanib to Delay Disease Progression in Patients With Metastatic Clear Cell Renal Cell Cancer The ROPETAR Randomized Clinical Trial
| Autor: | Martijn P. Lolkema, Marco B. Polee, Olaf Loosveld, Paul Hamberg, Geert A. Cirkel, Stefan Sleijfer, Heinz-Josef Klümpen, Johanna E.A. Portielje, Emile E. Voest, Frank P. J. Peters, Vincent van der Noort, Gerard Groenewegen, Maartje Los, Maureen J.B. Aarts, Franchette W P J van den Berkmortel, Laurens V. Beerepoot, John B. A. G. Haanen, Metin Tascilar, M. Wouter Dercksen |
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| Přispěvatelé: | Oncology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Medical Oncology, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research Kaplan-Meier Estimate GUIDELINES THERAPY law.invention 0302 clinical medicine Randomized controlled trial Renal cell carcinoma law Antineoplastic Combined Chemotherapy Protocols Clinical endpoint Aged 80 and over Sulfonamides PHASE-III TRIAL Middle Aged Kidney Neoplasms 030220 oncology & carcinogenesis Disease Progression Female medicine.drug Adult medicine.medical_specialty Indazoles CARCINOMA Disease-Free Survival Pazopanib 03 medical and health sciences SDG 3 - Good Health and Well-being Internal medicine SURVEILLANCE medicine Carcinoma Mucositis Humans Everolimus SUNITINIB RECHALLENGE Carcinoma Renal Cell Aged DRUG-RESISTANCE business.industry medicine.disease EFFICACY Surgery Clear cell renal cell carcinoma 030104 developmental biology Pyrimidines Quality of Life business |
| Zdroj: | JAMA oncology, 3(4), 501-508. American Medical Association JAMA Oncology, 3(4), 501-508. American Medical Association |
| ISSN: | 2374-2437 2374-2445 |
| Popis: | Importance To our knowledge, this is the first randomized clinical trial evaluating an alternating treatment regimen in an attempt to delay disease progression in clear cell renal cell carcinoma. Objective To test our hypothesis that an 8-week rotating treatment schedule with pazopanib and everolimus delays disease progression, exhibits more favorable toxic effects, and improves quality of life when compared with continuous treatment with pazopanib. Design, Setting, and Participants This was an open-label, randomized (1:1) study (ROPETAR trial). In total, 101 patients with treatment-naive progressive metastatic clear cell renal cell carcinoma were enrolled between September 2012 and April 2014 from 17 large peripheral or academic hospitals in The Netherlands and followed for at least one year. Interventions First-line treatment consisted of either an 8-week alternating treatment schedule of pazopanib 800 mg/d and everolimus 10 mg/d (rotating arm) or continuous pazopanib 800 mg/d (control arm) until progression. After progression, patients made a final rotation to either pazopanib or everolimus monotherapy (rotating arm) or initiated everolimus (control arm). Main Outcome and Measures The primary end point was survival until first progression or death. Secondary end points included time to second progression or death, toxic effects, and quality of life. Results A total of 52 patients were randomized to the rotating arm (median [range] age, 65 [44-87] years) and 49 patients to the control arm (median [range] age, 67 [38-82] years). Memorial Sloan Kettering Cancer Center risk category was favorable in 26% of patients, intermediate in 58%, and poor in 15%. Baseline characteristics and risk categories were well balanced between arms. One-year PFS1 for rotating treatment was 45% (95% CI, 33-60) and 32% (95% CI, 21-49) for pazopanib (control). Median time until first progression or death for rotating treatment was 7.4 months (95% CI, 5.6-18.4) and 9.4 months (95% CI, 6.6-11.9) for pazopanib (control) ( P = .37). Mucositis, anorexia, and dizziness were more prevalent in the rotating arm during first-line treatment. No difference in quality of life was observed. Conclusions and Relevance Rotating treatment did not result in prolonged progression-free-survival, fewer toxic effects, or improved quality of life. First-line treatment with a vascular endothelial growth factor inhibitor remains the optimal approach in metastatic clear cell renal cell carcinoma. Trial Registration clinicaltrials.gov Identifier:NCT01408004 |
| Databáze: | OpenAIRE |
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