Advertisement

Advances in Therapy

, Volume 36, Issue 12, pp 3446–3457 | Cite as

Real-World Effectiveness and Tolerability of Pazopanib as First Targeted Therapy in Metastatic Renal Cell Carcinoma: A Retrospective Chart Review in Latin America

  • David Queiroz MunizEmail author
  • Barbara Ratto
  • Hongbo Yang
  • Jing Zhao
  • Madeline Jenkins
  • James Signorovitch
  • Luca Dezzani
  • Pamela Salman
  • Mauricio Lema Medina
  • Diego Lopera
  • Guillermo Lerzo
  • Cesar del Castillo
  • Matias Chacon
  • Ana Martin
  • Saul Campos-Gomez
Original Research

Abstract

Introduction

Pazopanib is approved in Latin America as first targeted therapy for patients with metastatic renal cell carcinoma (mRCC).

Methods

A retrospective chart review of adult patients with mRCC who initiated pazopanib as first targeted therapy between January 2011 and March 2016 was conducted among oncology care centers in Argentina, Brazil, Chile, Colombia, and Mexico. Patient characteristics, treatment patterns, overall survival (OS), progression-free survival (PFS), and adverse events were summarized.

Results

A total of 156 charts of patients with mRCC receiving first-line pazopanib were reviewed (29, 54, 27, 28, and 18 patients from Argentina, Brazil, Chile, Colombia, and Mexico, respectively). The mean age at initial mRCC diagnosis was 61.6 years, 73.7% were male, and 51.3% were Hispanic. The median dose of pazopanib was 800 mg and the median time from initial mRCC diagnosis to pazopanib start was 2.2 months. The median time on treatment was 10.0 months. At the time of data extraction, 16.7% of patients remained on pazopanib, with clinical progression listed as the main reason for discontinuation. Subsequent therapy was received by 25.6% of patients; the most common were everolimus (9.6%) and axitinib (5.8%). Overall, median PFS and OS were 10.8 and 16.9 months, respectively, and varied across countries. The most common all-grade adverse events were diarrhea (44.9%), asthenia/fatigue (43.6%), and nausea (28.8%).

Conclusions

Pazopanib was used for first-line mRCC treatment in a clinically diverse patient population across Latin America. Real-world PFS and tolerability were similar to clinical studies of pazopanib.

Funding

Novartis Pharmaceuticals Corporation, Inc.

Keywords

Chart review Latin America Metastatic renal cell carcinoma Pazopanib Real world 

Notes

Acknowledgements

We would like to thank the patients and their families for participating in the studies, as well the site investigators and staff who assisted with the study.

Funding

Sponsorship for this study and the journal’s Rapid Service Fee were funded by Novartis Pharmaceuticals Corporation, Inc. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Medical Writing, Editorial, and Other Assistance

Medical writing assistance for this article was provided by Shelley Batts, Ph.D. a professional medical writer employed by Analysis Group, Inc. Editorial assistance was provided by Rakesh Khuntia, an employee of Novartis Healthcare Private Limited. Support for this assistance was funded by Novartis Pharmaceuticals Corporation, Inc.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Prior Presentation

This work was previously presented as an abstract at the Seventeenth International Kidney Cancer Symposium, Miami, Florida.

Disclosures

David Queiroz Muniz provides research and clinical consultation for Novartis Pharmaceuticals Corporation, Inc. Barbara Ratto is an employee of Novartis Pharmaceuticals Corporation, Inc. and declares ownership of stock/stock options from Novartis Pharmaceuticals Corporation, Inc. Hongbo Yang is an employee of Analysis Group, Inc., which received payment from Novartis Pharmaceuticals Corporation, Inc. for contracted research. Jing Zhao is an employee of Analysis Group, Inc., which received payment from Novartis Pharmaceuticals Corporation, Inc. for contracted research. Madeline Jenkins is an employee of Analysis Group, Inc., which received payment from Novartis Pharmaceuticals Corporation, Inc. for contracted research. James Signorovitch is an employee of Analysis Group, Inc., which received payment from Novartis Pharmaceuticals Corporation, Inc. for contracted research. Luca Dezzani is an employee of Novartis Pharmaceuticals Corporation, Inc. at the time of the study conduct. Pamela Salman provides research and clinical consultation for Novartis Pharmaceuticals Corporation, Inc. Mauricio Lema Medina provides research and clinical consultation for Novartis Pharmaceuticals Corporation, Inc. Diego Lopera provides research and clinical consultation for Novartis Pharmaceuticals Corporation, Inc. Guillermo Lerzo provides research and clinical consultation for Novartis Pharmaceuticals Corporation, Inc. Cesar del Castillo provides research and clinical consultation for Novartis Pharmaceuticals Corporation, Inc. Matias Chacon provides research and clinical consultation for Novartis Pharmaceuticals Corporation, Inc. Ana Martin provides research and clinical consultation for Novartis Pharmaceuticals Corporation, Inc. Saul Campos-Gomez provides research and clinical consultation for Novartis Pharmaceuticals Corporation, Inc.

Compliance with Ethics Guidelines

The study was reviewed and approved by the institutional review boards of the participating oncology care centers in the five Latin American countries as follows: Brazil (Instituto do Câncer do Estado de São Paulo: July 10, 2017; Brazilian National Cancer Institute: June 3, 2018), Argentina (Fleming Institute: February 3, 2017; Centro Medico Lucen: January 25, 2017), Colombia (Astorga Clínica de Oncología: January 26, 2017; Oncologos de Occidente: February 6, 2017); Mexico (Centro Oncológico Estatal: September 11, 2017; Centro Médico Nacional Siglo XXI: December 7, 2017), and Chile (Hospital San Borja: June 1, 2017; Fundacion Arturo Lopez: May 16, 2017). This study conforms with the Helsinki Declaration of 1964, as revised in 2013, concerning human rights.

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available due to confidentiality of the patient data.

References

  1. 1.
    Azeem K, Kollarova H, Horakova D, Magnuskova S, Janout V. Genetic syndromes associated with renal cell carcinoma: a review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011;155(3):231–8.CrossRefGoogle Scholar
  2. 2.
    Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev. 2008;34(3):193–205.CrossRefGoogle Scholar
  3. 3.
    Surveillance Epidemiology and End Results (SEER). SEER stat fact sheets: kidney and renal pelvis cancer. 2019. http://seer.cancer.gov/statfacts/html/kidrp.html. Accessed 18 Feb 2019.
  4. 4.
    Thompson RH, Ordonez MA, Iasonos A, et al. Renal cell carcinoma in young and old patients—is there a difference? J Urol. 2008;180(4):1262–6 (discussion 6).CrossRefGoogle Scholar
  5. 5.
    Wiechno P, Kucharz J, Sadowska M, et al. Contemporary treatment of metastatic renal cell carcinoma. Med Oncol. 2018;35(12):156.CrossRefGoogle Scholar
  6. 6.
    Flanigan RC, Campbell SC, Clark JI, Picken MM. Metastatic renal cell carcinoma. Curr Treat Options Oncol. 2003;4(5):385–90.CrossRefGoogle Scholar
  7. 7.
    Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med. 1996;335(12):865–75.CrossRefGoogle Scholar
  8. 8.
    Surveillance, Epidemiology, and End Results (SEER) Program. 2018. https://seer.cancer.gov/. Accessed 1 Apr 2019.
  9. 9.
    Ljungberg B, Campbell SC, Choi HY, et al. The epidemiology of renal cell carcinoma. Eur Urol. 2011;60(4):615–21.CrossRefGoogle Scholar
  10. 10.
    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefGoogle Scholar
  11. 11.
    Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650–61.CrossRefGoogle Scholar
  12. 12.
    US National Library of Medicine. BI 655066/ABBV-066 (risankizumab) in moderate to severe plaque psoriasis with randomized withdrawal and re-treatment [ClinicalTrials.gov Identifier: NCT02672852]. 2018. https://clinicaltrials.gov/ct2/show/NCT02672852. Accessed 1 Apr 2019.
  13. 13.
    Ferlay JSI, Ervik M, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon: International Agency for Research on Cancer. 2013. http://globocan.iarc.fr. Accessed 18 Mar 2014.
  14. 14.
    Ríos MAJ, Cervera PM, Ponce JLA, et al. Oncoguía: Cáncer Renal [OncoGuide: Kidney Cancer]. Cancerología. 2011;6:19–24.Google Scholar
  15. 15.
    Pardo C, Cendales R. Incidencia, mortalidad y prevalencia de cáncer en Colombia, 2007–2011 (incidence, mortality and prevalence of cancer in Colombia, 2007–2011). Bogota: Instituto Nacional de Cancerología-ESE; 2015.Google Scholar
  16. 16.
    Mirra APLM, Veneziano DB. Incidência de Câncer no Município de São Paulo, Brasil 1997–1998: mortalidade de Câncer no Município de São Paulo, Brasil: tendência no Período de 1969–1998 [Cancer incidence in São Paulo, Brazil 1997–1998: Cancer mortality in São Paulo, Brazil: trend in the period 1969–1998]. Brasília: Ministério da Saúde; 2001.Google Scholar
  17. 17.
    American Cancer Society. Key statistics about kidney cancer. 2019. http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-key-statistics. Accessed 22 Feb 2019.
  18. 18.
    Atkins MB, Choueiri TK. Epidemiology, pathology, and pathogenesis of renal cell carcinoma. UpToDate. 2019. https://www.uptodate.com/contents/epidemiology-pathology-and-pathogenesis-of-renal-cell-carcinoma. Accessed 22 Feb 2019.
  19. 19.
    Linehan WMBS, Yang JC. Cancers of the genitorurinary system: cancer of the kidney. In: Devita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 7th ed. Philadelphia: Lippincott; 2006. p. 1139–68.Google Scholar
  20. 20.
    Smaletz O. Current management and future directions in the treatment of advanced renal cell carcinoma-a Latin American perspective: 10 years in review. Int Braz J Urol. 2015;41(5):835–43.CrossRefGoogle Scholar
  21. 21.
    Cella D, Beaumont JL. Pazopanib in the treatment of advanced renal cell carcinoma. Ther Adv Urol. 2016;8(1):61–9.CrossRefGoogle Scholar
  22. 22.
    Sternberg CN, Hawkins RE, Wagstaff J, et al. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013;49(6):1287–96.CrossRefGoogle Scholar
  23. 23.
    Hutson TE, Davis ID, Machiels JP, et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010;28(3):475–80.CrossRefGoogle Scholar
  24. 24.
    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(6):1061–8.CrossRefGoogle Scholar
  25. 25.
    Abreu D, Gueglio G, Garcia P, et al. Outcomes in over 4000 patients with renal cell carcinoma from the Latin American Renal Cancer Group (LARCG): a focus on metastatic disease: MP16-17. J Urol. 2017;197(4):e186.Google Scholar
  26. 26.
    Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369(8):722–31.CrossRefGoogle Scholar
  27. 27.
    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(4):491–7.CrossRefGoogle Scholar
  28. 28.
    Bergerot PG, Bergerot CD, Dizman N, et al. Assessment of treatment patterns for metastatic renal cell carcinoma in Brazil. J Glob Oncol. 2017;4:1–8.PubMedGoogle Scholar
  29. 29.
    Escudier B, Bellmunt J, Negrier S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010;28(13):2144–50.CrossRefGoogle Scholar
  30. 30.
    Rini BI, Halabi S, Rosenberg JE, et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010;28(13):2137–43.CrossRefGoogle Scholar

Copyright information

© Springer Healthcare Ltd., part of Springer Nature 2019

Authors and Affiliations

  • David Queiroz Muniz
    • 1
    Email author
  • Barbara Ratto
    • 2
  • Hongbo Yang
    • 3
  • Jing Zhao
    • 3
  • Madeline Jenkins
    • 3
  • James Signorovitch
    • 3
  • Luca Dezzani
    • 2
  • Pamela Salman
    • 4
  • Mauricio Lema Medina
    • 5
  • Diego Lopera
    • 6
  • Guillermo Lerzo
    • 7
  • Cesar del Castillo
    • 8
  • Matias Chacon
    • 9
  • Ana Martin
    • 10
  • Saul Campos-Gomez
    • 11
  1. 1.Instituto do Câncer do Estado de São PauloSão PauloBrazil
  2. 2.NovartisEast HanoverUSA
  3. 3.Analysis Group Inc.BostonUSA
  4. 4.Fundación Arturo López PérezSantiagoChile
  5. 5.Clínica de OncologíaMedellínColombia
  6. 6.Oncólogos de OccidentePereiraColombia
  7. 7.Centro Medico LucenBuenos AiresArgentina
  8. 8.Hospital San Borja ArriaránSantiagoChile
  9. 9.Fleming InstituteBuenos AiresArgentina
  10. 10.Hospital de Oncología de Centro Médico Nacional Siglo XXIMexico CityMexico
  11. 11.Centro Oncológico Estatal, ISSEMyMToluca de LerdoMexico

Personalised recommendations