From today, patients in England and Wales living with advanced renal cell carcinoma, a type of kidney cancer, can access Votrient® (pazopanib) on the National Health Service (NHS).1 The National Institute for Health and Clinical Excellence (NICE) has issued positive final guidance (known as Technology Appraisal Guidance - (TAG) for Votrient, a targeted oral treatment, which has been shown to effectively slow down disease progression whilst maintaining quality of life compared with placebo.1

Professor Robert Hawkins, Consultant Medical Oncologist at The Christie, Manchester commented on NICE's final guidance: "This decision means clinicians will be able to offer their patients a choice of first-line, oral treatments for advanced renal cell carcinoma, each with different side effect profiles. Pazopanib's positive guidance from NICE allows patients in England and Wales to access an additional treatment, which can control their kidney cancer whilst maintaining quality of life - an important consideration for patients at the advanced stage of disease."

Advanced renal cell carcinoma is an aggressive form of kidney cancer, which is generally unresponsive to chemotherapy, radiotherapy and hormonal therapy.2,3 Targeted therapies have transformed the effective management of renal cell carcinoma,4-6 but until today, only one such treatment has been available on the NHS.7 NICE acknowledged that there are limited treatment options and that pazopanib would be a useful first-line treatment option for patients with advanced RCC.1

The NICE TAG recommends pazopanib as a first-line treatment option for people with advanced renal cell carcinoma who have not previously received cytokine therapy and who are of Eastern Cooperative Oncology Group (ECOG) performance status 0-1, on the basis that GSK provides the agreed patient access scheme.1 The access scheme offers a straight discount at the point of invoice and makes provision for a possible partial rebate to the NHS in the future, conditional upon the outcome of the ongoing head-to-head trial versus sunitinib, the current standard-of-care (the COMPARZ trial).

Patients can often suffer delays in being able to access innovative cancer medicines, as the full clinical value typically evolves over time as further studies on the treatment's benefits are completed. GlaxoSmithKline (GSK) believes that patients should be able to access these treatments as soon as they are available, and to facilitate this, proposed an innovative and flexible approach to pricing.1 GSK proposed to NICE a potential partial rebate, conditional upon the outcome of the COMPARZ trial.1 GSK is confident that the appropriate evidence will be generated but if not, GSK will pay the NHS a partial rebate.

Simon Jose, General Manager, GSK UK welcomes the positive decision from NICE: "Advanced kidney cancer is a devastating disease and we are pleased that through this pricing scheme we are able to offer patients rapid access to Votrient whilst delivering value for money to the NHS."

Notes

About Votrient (pazopanib)

Pazopanib is a new, selective,8,9 oral treatment which effectively slows down the progression of advanced renal cell carcinoma whilst maintaining patients' quality of life (QoL) compared with placebo, as shown by the mean change from baseline in QoL scores.10-12 Pazopanib was granted a conditional marketing authorisation by the EMA in June 2010 and is indicated for the first-line treatment of advanced renal cell carcinoma and for patients who have received prior cytokine therapy for advanced disease.12 The licence is conditional upon the outcome of the ongoing head-to-head study versus sunitinib.

Pazopanib is a type of medicine called a tyrosine kinase inhibitor (TKI). It works by inhibiting angiogenesis (the process of developing new blood vessels), thereby slowing tumour growth and the spread of cancer to another part of the body.8-10,13,14

The majority of adverse events experienced by patients on pazopanib are mild to moderate (grades 1 and 2).10,12 The most frequent adverse events related to pazopanib treatment (all grade incidence ≥20%) are diarrhoea, hair colour changes, hypertension, nausea, fatigue, anorexia and increased liver enzymes.10,12 There was a low incidence of hand-foot syndrome, mucositis/stomatitis and fatigue adverse events occurring with grade 3/4 severity.10,12 Liver enzyme increases associated with pazopanib were largely reversible and can be identified by regular liver function monitoring and dose modification as necessary.10,12 Please refer to the Summary of Product Characteristics for further information on dosing and special warnings/contraindications associated with pazopanib.

Pazopanib pivotal clinical trial data

The pivotal double blind, multicentre phase III study (VEG 105192) was undertaken in 435 patients with advanced renal cell carcinoma who had received no prior drug treatment (n=233) or who had failed on a cytokine-based regimen (n=202).10 The study investigated the safety and efficacy of pazopanib compared with a placebo (plus best supportive care).10 Results showed that pazopanib significantly increased the time that patients remained progression-free (defined as the time without further tumour growth or death due to any cause) by 54% compared with placebo, in the overall study population comprising both treatment naïve and cytokine pre-treated patients.10 In this combined population, pazopanib showed 9.2 months progression-free survival (PFS) compared with 4.2 months on placebo (p<0.0001).10 In the first-line treatment of patients who had received no previous therapy for advanced renal cell carcinoma, PFS was significantly increased with pazopanib compared with placebo (11.1 months vs. 2.8 months; p<0.0001), equating to a 60% reduction in the risk of disease progression with pazopanib compared to placebo.10

A final analysis of overall survival (OS) found a median OS of 22.9 months for pazopanib-treated patients compared with 20.5 months for those on placebo in the overall study population.15 This analysis is confounded by the early, high rate and prolonged duration of cross-over of patients randomised to placebo to another anti-cancer treatment following disease progression. Approximately twice as many patients in the placebo arm received subsequent anti-cancer therapies than in the pazopanib arm (66% vs 30%), with 54% of placebo patients crossing over to receive pazopanib, some as early as six weeks.15 Analyses conducted to adjust for the effect of cross-over/post-study therapy suggest that there is a 50% to 57% reduction in risk of death associated with pazopanib compared with placebo in the overall study population.15

The majority of adverse events experienced by patients on pazopanib in the pivotal clinical trial were mild to moderate (grades 1 and 2); the most common being diarrhoea, hypertension, hair colour changes, nausea, anorexia and vomiting.10 There was a low incidence of hand-foot syndrome, mucositis/stomatitis and fatigue adverse events occurring with grade 3/4 severity.10 The most common laboratory abnormalities associated with pazopanib were liver enzyme elevations, which were largely reversible and can be managed through regular liver function monitoring and dose modification as necessary.12 Serious adverse events with an incidence of less than 1% have also been reported in association with pazopanib.10,12 Further information can be found in the Summary of Product Characteristics.

About the NICE Technology Appraisal Guidance

The ECOG is a scale used by doctors to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient and used by doctors to determine appropriate treatment and prognosis. An ECOG performance status score of 0 or 1 is an indicator of good prognosis, which means that the patient is relatively healthy and well given the status of their disease. This is the same patient population as those enrolled in the pazopanib and sunitinib phase III clinical trials.

About the Pazopanib Patient Access Scheme

In order to make pazopanib accessible to patients quickly, GSK has offered an innovative patient access scheme, which includes a straight 12.5% discount on the list price at the point of invoice and a potential partial rebate in the future, linked to the outcome of a head-to-head trial against the current standard of care (sunitinib).1 The head-to-head study versus sunitinib (COMPARZ) is currently underway and is due to report in 2012.16 GSK is confident that the evidence from this trial will demonstrate the full value of pazopanib, but, if it does not, will pay a partial rebate to the NHS.

About renal cell carcinoma (RCC)

Renal cell carcinoma accounts for over 80% of kidney cancers in the UK.17 Worldwide and UK incidence, as well as mortality from renal cell carcinoma, is increasing.18 In the UK, in 2007, there were approximately 8,228 people diagnosed with kidney cancer and in 2008 it is estimated that 3,848 people died of the disease.19

References

1. NICE. Pazopanib for the treatment of patients with advanced renal-cell carcinoma. Technology appraisal guidance document. See here. Accessed February 2011.

2. Ljungberg B, Hanbury D, Kuczyk M et al. Renal Cell Carcinoma Guideline. 2007; 51: 1502 - 1510.

3. Gupta K et al. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev 2008; 34: 193-205.

4. Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma. N Engl Med 2007; 356: 115-24.

5. Escudier B, Pluzanska A, Koralewski P et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007; 370: 2103-2111.

6. 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.

7. NICE. Sunitinib for the first-line treatment of advanced and/or metastatic renal cell carcinoma. NICE technology appraisal guidance 169. March 2009.

8. Karaman MW, Herrgard S, Treiber DK et al.A quantitative analysis of kinase inhibitor selectivity. Nature Biotechnology 2008; 26: 127-132.

9. Kumar R, Crouthamel MC, Romniger DH et al. Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors. Br J Cancer 2009; 101: 1717-1723.

10. Sternberg CN, Davis ID, Mardiak J et al. Pazopanib in locally advanced and/or metastatic renal cell carcinoma: results of a randomized Phase III trial. J Clin Oncol 2010; 28: 1061-1068.

11. Hawkins R, Hodge R, Chen M et al. Quality of Life (QOL) in treatment-naive and cytokine pretreated patients with advanced renal cell carcinoma (RCC) treated with pazopanib: results from a Phase III double-blind, placebo-controlled trial 2009 ECCO-ESMO Poster Number 132.

12. Votrient Summary of Product Characteristics (SPC). GlaxoSmithKline, June 2010.

13. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005; 23:1011-1027.

14. Sonpavde G, Hutson TE. Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep 2007; 9: 115-119.

15. Sternberg CN, Hawkins RE, Szczylik C, et al. Randomized, double-blind phase III study of Votrient in patients with advanced/metastatic renal cell carcinoma (mRCC): final overall survival (OS) results. Abstract and oral presentation at 35th European Society of Medical Oncology Congress, October 2010. Abstract no. LBA22.

16. Study VEG108844, a Study of Pazopanib Versus Sunitinib in the Treatment of Subjects with locally advanced and/or metastatic renal cell carcinoma (COMPARZ). Received: July 2008.

17. Cancer Research UK: Types of kidney cancer. Available here. Accessed December 2010.

18. Cancer Research UK: Kidney cancer - UK incidence statistics. Available here. Accessed December 2010.

19. Cancer Research UK: Kidney cancer statistics UK. Available here. Accessed December 2010.

Source:
GlaxoSmithKline