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Pazopanib: A Formulary Dossier

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Pazopanib: A Formulary Dossier

  1. 1. PazopanibFormulary DossierBy Joseph Feliciano
  2. 2. Renal Cell Carcinoma• Occurs most commonly in patients over the age of 45, with the average age of diagnosis being 65 • overall lifetime risk is 1.5%, with the risk being 2-fold greater in men • 64,770 new cases every year • 40,250 in men, 24,520 in women13,570 deaths (8,650 in men, 4,920 in women)• Patients present with : • abdominal pain • hematuria and a palpable mass in either the abdomen or flank area • Diagnosis is confirmed via an abdominal CT scan • 20 to 30% of cases have already metastasized to other areas, often including the lungs, bone, liver and brain at diagnosis • Risk Factors • Smoking • Advanced kidney disease • Obesity • long term use of high dose • Exposure to diuretics pesticides, cleaning • familial history/Genetic agents or asbestos
  3. 3. PRODUCT INFORMATION• Pazopanib (VotrientTM) • FDA Labeled Indication • Approved by the FDA on • Renal cell carcinoma October 19, 2009 • Off Label Uses • Therapeutic Class and AHFS Classification • Nasopharyngeal Carcinoma • Oral Tyrosine Kinase • Hepatocellular Carcinoma Inhibitor/ Anti-neoplastic • Thyroid Cancer agent • Metastatic Breast Cancer • AWP and WAC: $7408.16 and • Recurrent Glioblastoma $ 6173.47 • Ovarian Cancer • AWP per Unit Cost: $61.73
  4. 4. Pharmacology
  5. 5. Place Of Product In Therapy• National Cancer Center Network Recommendations Regarding RCC – Stages I-III • Partial nephrectomy as first-line therapy for localized tumors • Radical nephrectomy, including resection of the accompanying adrenal gland – Both surgical options may or may not include palliative radiation – Stage IV metastatic disease – First Line Therapy • Cytokine therapy – Interleukin-2 and interferon alpha • Targeted therapy – Pazopanib – Sunitinib – Bevacizumab
  6. 6. Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial• Research Goal • To evaluate safety and efficacy of pazopanib in treatment naïve patients and those who previously received systemic cytokine therapy • Trial Design • Placebo controlled, randomized double blind, global, multicenter, Phase III study • Randomization • Based on: • ECOG PS (1 vs. 0) • prior nephrectomy ( y vs. n) • prior systemic treatment
  7. 7. Pazopanib in Locally Advanced or Metastatic Renal CellCarcinoma: Results of a Randomized Phase III Trial (continued)• Inclusion criteria – Documented RCC, treatment naïve or received systemic cytokine therapy, measurable disease per Response Criteria in Solid Tumors, age >/18, ECOG PS </ 1, adequate hepatic, renal and hematologic function.• Exclusion criteria – CNS metastases, leptomeningeal lesions, or any of the following within 6 months of screening: • uncontrolled HTN, QTc prolongation >/470ms, history of class III/IV CHF, MI or unstable angina, angioplasty or stenting, or CVA• Participant Demographics – Treatment naïve patients or patients who have received systemic therapy – 435 total patients, median age for treatment or placebo was 60, – 68% of treatment group and 75% of placebo group were men, – 87% of TG and 84% of P were white – Median time to initial diagnosis was 15.7 and 13.8 months
  8. 8. Pazopanib in Locally Advanced or Metastatic Renal CellCarcinoma: Results of a Randomized Phase III Trial (continued)• Outcomes Measure – Primary endpoint: progression free survival • Secondary endpoints: Overall survival, complete response, partial response, duration of response, and health related quality of life• Results – PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P < .0001) • The treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001) • The cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001) – The objective response rate was 30% with pazopanib compared with 3% with placebo (P <.001) – The median duration of response was longer than 1 year – The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting
  9. 9. Pazopanib: An Oral Multi-targeted Tyrosine Kinase Inhibitor for Use in Renal Cell Carcinoma• Research Goal – To evaluate the available clinical data available on pazopanib, as well as review the merit and adverse events of using pazopanib in RCC• Trial Design – Systematic primary literature search• Inclusion/Exclusion Criteria – All available English-language articles and trials that described the pharmacokinetics, pharmacology, pharmacodynamics, clinical activity, or adverse effects of pazopanib were reviewed• Participant Demographics – Phase 2 trial: 225 patients that either received prior systemic treatment with cytokines alone, cytokines with Avastin, or treatment naïve – Phase 3 trial: Previously covered – Toxicity study: 977 patients that were taking pazopanib for a median time of 7.5 months
  10. 10. Pazopanib: An Oral Multi-targeted Tyrosine Kinase Inhibitor for Use in Renal Cell Carcinoma (continued)• Outcomes Measured – Progression free survival – Overall survival – Rates of toxicity and adverse events (all grades)• Results – Reported Results from phase III trial – Reported incidences of toxicities and their associate adverse events • Determined how safe it is use to pazopanib in the treatment of mRCC
  11. 11. Economic evaluation of new targeted therapies for the first- line treatment of patients with metastatic renal cell carcinoma• Research Goal – To assess the cost effectiveness and cost utility of sunitinib malate as a first-line treatment in metastatic renal cell carcinoma (mRCC) compared with IFN-alpha and interleukin-2• Perspective – Presented from a U.S. and Swedish third party payor perspective• Study Design – A Markov model simulated disease progression, adverse events and survival with sunitinib vs sorafenib in the US and bevacizumab plus interferon- alpha and to analyze the associated costs.
  12. 12. Economic evaluation of new targeted therapies for the first-line treatment of patients with metastatic renal cell carcinoma (Continued)• Cost
  13. 13. Economic evaluation of new targeted therapies for the first-line treatment of patients with metastatic renal cell carcinoma (Continued) • Results
  14. 14. Economic evaluation of sunitinib malate for the first-line treatment of metastatic renal cell carcinoma• Research Goal – To compare cost-effectiveness of three new targeted therapies in mRCC head-to-head • Based on indirect comparison of clinical efficacy• Perspective – U.S. societal perspective• Study Design – A Markov model was developed to simulate disease progression and to determine progression- free survival, total life-years (LYs), and quality-adjusted life- years (QALYs) gained.
  15. 15. Economic evaluation of sunitinib malate for the first-line treatment of metastatic renal cell carcinoma (continued)• Costs
  16. 16. Economic evaluation of sunitinib malate for the first-line treatment of metastatic renal cell carcinoma (continued)• Results
  17. 17. Conclusions• Clinical Benefit – As a First Line Option • Can be used in newly diagnosed or previously treated patients, safely – Noted to cause hepatotoxicity, hypertension, and gastrointestinal discomfort • Difficult to differentiate between pazopanib and sunitinib – Matter of preference for the physician• Economic Benefit – Difficult to assess due to the lack of data • Used a comparable drug in efficacy, adverse events, and associated costs• Recommendations – Non-preferred agent • Used only as step up treatment or due to a complete contraindication – Reevaluate when: • the head to head study between pazopanib and sunitinib in mRCC is complete • More economic data on pazopanib is released
  18. 18. ReferencesBenedict, Agnes. "Economic Evaluation of New Targeted Therapies for theFirst-line Treatment of Patients with Metastatic Renal Cell Carcinoma."British Journal of Urology International (2011). Web.Biocarta. Web. <http://www.biocarta.com/pathfiles/h_vegfpathway.asp>.LaPlant, K. D., and P. D. Louzon. "Pazopanib: An Oral Multitargeted Tyrosine Kinase Inhibitor for Use in Renal Cell Carcinoma." Annals of Pharmacotherapy 44.6 (2010): 1054-060. Print.Remak, E., C. Charbonneau, S. Negrier, S. T. Kim, and R. J. Motzer. "Economic Evaluation of Sunitinib Malate for the First-Line Treatment of MetastaticRenal Cell Carcinoma." Journal of Clinical Oncology 26.24 (2008): 3995-4000. Web.Sternberg, Cora Anne. "Journal of Clinical Oncology." Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial. Web. 01 Apr. 2012.<http://jco.ascopubs.org/content/28/6/1061>.

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