First-line pazopanib in intermediate- and poor-risk patients with metastatic renal cell carcinoma: Final results of the FLIPPER trial.
Administration, Oral
Adult
Aged
Aged, 80 and over
Angiogenesis Inhibitors
/ administration & dosage
Carcinoma, Renal Cell
/ drug therapy
Diarrhea
/ chemically induced
Fatigue
/ chemically induced
Female
Humans
Hypothyroidism
/ chemically induced
Indazoles
/ administration & dosage
Kaplan-Meier Estimate
Kidney Neoplasms
/ drug therapy
Male
Middle Aged
Nausea
/ chemically induced
Neoplasm Metastasis
Pyrimidines
/ administration & dosage
Sulfonamides
/ administration & dosage
Treatment Outcome
overall survival
pazopanib
poor-risk patients
progression-free survival
renal cell carcinoma
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 02 2021
15 02 2021
Historique:
received:
17
12
2019
revised:
30
06
2020
accepted:
07
07
2020
pubmed:
2
8
2020
medline:
13
7
2021
entrez:
2
8
2020
Statut:
ppublish
Résumé
Temsirolimus has long been the only approved first-line standard of care (SOC) with overall survival (OS) benefit in poor-risk patients with advanced or metastatic renal cell cancer (mRCC). However, tyrosine kinase inhibitors are also commonly used in clinical practice. Pazopanib is an SOC for first-line mRCC treatment, but for poor-risk patients data are scarce. The FLIPPER (First-Line Pazopanib in Poor-Risk Patients with Metastatic Renal Cell Carcinoma) study aimed to assess efficacy and safety of first-line pazopanib in poor-risk mRCC patients. FLIPPER was a single-arm, multicenter, Phase IV trial. Key inclusion criteria were treatment-naive clear cell, inoperable advanced or mRCC, poor-risk according to MSKCC with slight modification, Karnofsky performance status (KPS) ≥60% and adequate organ function. Oral pazopanib 800 mg was given daily. Primary endpoint was the 6-month progression-free survival rate (PFS6). Secondary endpoints included PFS, OS, overall response rate (ORR), duration of response (DOR) and safety. For analysis, descriptive statistics were used. Between 2012 and 2016, 60 patients had been included. Forty-three patients qualified for safety analyses, 34 for efficacy. Median age was 66 years, 64.7% of patients were poor-risk, 82.4% had a KPS ≤70%. PFS6 was 35.3% (95% CI, 19.7-53.5). Median PFS and OS were 4.5 months (95% CI, 3.6-7.8) and 9.3 months (95% CI, 6.6-22.2), respectively. ORR was 32.4% (95% CI, 17.4-50.5), median DOR 9.7 months (95% CI, 1.8-12.4). The most common treatment-related grade 3/4 adverse event reported in 4.7% of patients was hypertension. No treatment-related death occurred. Since pazopanib is active and well tolerated in poor-risk patients with clear cell mRCC, our results support its use as first-line treatment in this setting.
Substances chimiques
Angiogenesis Inhibitors
0
Indazoles
0
Pyrimidines
0
Sulfonamides
0
pazopanib
7RN5DR86CK
Banques de données
ClinicalTrials.gov
['NCT01521715']
Types de publication
Clinical Trial, Phase IV
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
950-960Informations de copyright
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.
Références
Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356-387.
Flanigan RC, Campbell SC, Clark JI, Picken MM. Metastatic renal cell carcinoma. Curr Treat Options Oncol. 2003;4:385-390.
Leibovich BC, Blute ML, Cheville JC, et al. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. Cancer. 2003;97:1663-1671.
Cindolo L, Patard J-J, Chiodini P, et al. Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: a multicenter European study. Cancer. 2005;104:1362-1371.
Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002;20:289-296.
Mekhail TM, Abou-Jawde RM, Boumerhi G, et al. Validation and extension of the memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol. 2005;23:832-841.
Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271-2281.
Motzer RJ, Escudier B, Bukowski R, et al. Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma. Br J Cancer. 2013;108:2470-2477.
Motzer RJ, Jonasch E, Agarwal N, et al. Kidney cancer, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017;15:804-834.
Porta C, Tortora G, Larkin JM, Hutson TE. Management of poor-risk metastatic renal cell carcinoma: current approaches, the role of temsirolimus and future directions. Future Oncol. 2016;12:533-549.
Escudier B, Porta C, Schmidinger M, et al. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v58-v68.
Escudier B, Eisen T, Porta C, et al. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23:vii65-vii71.
Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28:1061-1068.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-247.
Kwitkowski VE, Prowell TM, Ibrahim A, et al. FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma. Oncologist. 2010;15:428-435.
European Medicines Agency - Find medicine - Votrient [Internet]. [cited July 25, 2018]; Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001141/human_med_001337.jsp&mid=WC0b01ac058001d124
Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369:722-731.
Pérez-Valderrama B, Arija A, A J, et al. Validation of the international metastatic renal-cell carcinoma database consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish oncologic genitourinary group (SOGUG) SPAZO study. Ann Oncol. 2016;27:706-711.
Goebell PJ, Müller L, Staehler M, et al. Prognostic factors for overall survival of patients with advanced renal cell carcinoma-data from the German prospective RCC-registry. Ann Oncol. 2017;28:v295-v329.
Tannir NM, Msaouel P, Ross JA, et al. Temsirolimus versus Pazopanib (TemPa) in patients with advanced clear-cell renal cell carcinoma and poor-risk features: A randomized phase II trial. Eur Urol Oncol. 2019;30079-3:S2588-S9311.
Motzer RJ, Hutson TE, McCann L, Deen K, Choueiri TK. Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. N Engl J Med. 2014;370:1769-1770.
Schmidinger M, Bamias A, Procopio G, et al. Prospective observational study of pazopanib in patients with advanced renal cell carcinoma (PRINCIPAL study). Oncologist. 2019;24:491-497.
Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus Sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 CABOSUN trial. J Clin Oncol. 2017;35:591-597.
Choueiri TK, Hessel C, Halabi S, et al. Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): progression-free survival by independent review and overall survival update. Eur J Cancer. 2018;94:115-125.
Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277-1290.
Heng DYC, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27:5794-5799.
Heng DY, Xie W, Regan MM, et al. External validation and comparison with other models of the international metastatic renal-cell carcinoma database consortium prognostic model: a population-based study. Lancet Oncol. 2013;14:141-148.
Escudier B, Porta C, Schmidinger M, et al. ESMO guidelines committee. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30:706-720.
Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27:3584-3590.
Escudier B, Porta C, Bono P, et al. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for Pazopanib versus Sunitinib in patients with metastatic renal cell carcinoma: PISCES study. J Clin Oncol. 2014;32:1412-1418.
Kim JH, Park I, Lee JL. Pazopanib versus sunitinib for the treatment of metastatic renal cell carcinoma patients with poor-risk features. Cancer Chemother Pharmacol. 2016;78:325-332.
Ruiz-Morales JM, Swierkowski M, Wells JC, et al. First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Eur J Cancer. 2016;65:102-108.
Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019;20:1370-1385.
Grünwald V. Patienten in der Studie CheckMate 214, die eine Erstlinienbehandlung beim fortgeschrittenen Nierenzellkarzinom mit Nivolumab + Ipilimumab oder Sunitinib wegen behandlungsbedingter unerwünschter Ereignisse abgebrochen haben (oral presentation). Jahrestagung der Deutschen, Österreichischen und Schweizerischen Gesellschaften für Hämatologie und Medizinische Onkologie (DGHO), Berlin, 2019.