NICE Recommends Votrient® (Pazopanib) For The First-Line Treatment Of Advanced Renal Cell Carcinoma (RCC)

Main Category: Cancer / Oncology
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 03 Jan 2011 - 0:00 PDT


Patients in England and Wales living with advanced kidney cancer (renal cell carcinoma - RCC) are one step closer to being able to access Votrient® (pazopanib), a targeted oral treatment, on the National Health Service (NHS). The National Institute for Health and Clinical Excellence (NICE) has issued the Final Appraisal Determination (FAD) recommending Votrient as a first-line treatment option for people with advanced RCC 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. The access scheme offers a straight discount and makes provision for a possible partial rebate to the NHS in the future, conditional upon the outcome of a head-to-head trial with current standard of care treatment.1

The introduction of targeted cancer therapies has transformed the management of advanced RCC.2-4 However, despite improvements in efficacy, side effects observed with available treatments to date can affect patients' quality of life and their ability to carry out normal daily activities.5-10 This was acknowledged by the NICE Appraisal Committee in their evaluation of evidence from the patient experts and clinicians. With only one targeted treatment option (sunitinib) recommended by NICE as a first-line treatment until now,11 the NICE recommendation of Votrient will offer patients and clinicians a choice of effective treatment options with different side-effect profiles.

Votrient has been shown to effectively slow down the progression of advanced RCC whilst maintaining QoL compared with placebo; a significant consideration for patients at an advanced stage of disease.12,13 Votrient has an acceptable and manageable toxicity profile. The most frequent adverse events related to Votrient treatment (all grade incidence ≥20%) are diarrhoea, hair colour change, hypertension, nausea, fatigue, anorexia and increased liver enzymes.12,14 There was a low incidence of grade 3/4 hand-foot syndrome, mucositis/stomatitis and fatigue.12

Professor Robert Hawkins, Consultant Medical Oncologist at The Christie, Manchester commented on the NICE decision. "We have had a major role in the trials of pazopanib and I welcome its approval by NICE for the treatment of patients with kidney cancer. This is a significant development for advanced kidney cancer patients living in England and Wales as it gives access to a further oral drug with a different side effect profile from that of other licensed agents. With pazopanib, patients have a chance to control their kidney cancer whilst maintaining quality-of-life and avoiding some of the side effects, which can be severe, that can occur with current treatments. The importance of today's decision, both from the point of view of patients and those treating them, should not be under-estimated."

Advanced RCC is an aggressive form of kidney cancer with a poor prognosis, due in part to its resistance to chemotherapy, radiotherapy and hormone therapy.15,16 Over 8,000 people in the UK are diagnosed with kidney cancer each year17 and around one third show signs of advanced RCC at the time of diagnosis.2,18,19

Simon Jose, General Manager, GlaxoSmithKline (GSK) UK commented: "NICE has acted quickly in recognising Votrient as a clinical and cost-effective treatment option for advanced kidney cancer. It is often difficult to demonstrate the full value of innovative cancer medicines initially, as the evidence driving that value typically evolves over time as further studies are completed. We recognise this challenge and that is why we have offered an innovative potential future value rebate scheme. We are confident that the ongoing head-to-head study will confirm the full value of Votrient in this setting, but, if not, we will pay a partial rebate to the NHS. This is great news for patients and physicians who can have rapid and equitable access to this treatment, good for the NHS as it delivers value for money and also allows GSK to achieve a fair return for its innovation."

Notes

About the NICE Final Appraisal Determination

The Final Appraisal Determination (FAD) recommends Votrient as a first-line treatment option for people with advanced RCC who have not previously received cytokine therapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.1

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 Votrient and sunitinib phase III clinical trials.

About Votrient

Votrient is a new, selective20,21 oral treatment which effectively slows down the progression of advanced RCC12 whilst maintaining patients' quality of life (QoL) compared with placebo, as shown by the mean change from baseline in QoL scores.12,13 Votrient was granted a conditional marketing authorisation by the EMA in June 2010 and is indicated for the first-line treatment of advanced RCC and for patients who have received prior cytokine therapy for advanced disease. The licence is conditional14 upon the outcome of the ongoing head-to-head study versus sunitinib.

Votrient 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.20-24 It also appears to have a different side effect profile from the other licensed protein TKIs in this setting.20,21,22,24

The most common adverse reactions (experienced by at least 10% of the patients of any grade) include: diarrhoea, hair colour change, hypertension, nausea, fatigue, anorexia, vomiting, dysgeusia, and elevated transaminases.12,14 There was a low incidence of grade 3/4 hand-foot syndrome, mucositis/stomatitis and fatigue.12 Serious adverse events with an incidence of <1% have also been reported with Votrient. Please refer to the prescribing information for further information on dosing and special warnings/contraindications associated with Votrient.14

Votrient data

A pivotal double blind, multicentre phase III study (VEG 105192) was undertaken in 435 patients with advanced RCC who had received no prior drug treatment (n=233) or who had failed on a cytokine-based regimen (n=202).12 The study investigated the safety and efficacy of Votrient compared with a placebo (plus best supportive care). Results showed that Votrient significantly increased the time that patients remained progression-free (defined as time without further tumour growth or death due to any cause) by 60 per cent compared with placebo in the first-line population comprising both treatment naïve and cytokine pre-treated patients.12 In this first-line population, Votrient showed 11.1 months progression free survival (PFS) compared with 2.8 months on placebo (p<0. 0001).12

The majority of adverse events experienced by patients on Votrient 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.12 There was a low incidence of grade 3/4 hand-foot syndrome, mucositis/stomatitis and fatigue.12 The most common laboratory abnormalities associated with Votrient were liver enzyme elevations, which were largely reversible and can be managed through regular liver function monitoring and dose modification as necessary.12,14 Serious adverse events with an incidence of less than 1 per cent have also been reported with Votrient.14 Further information can be found in the Summary of Product Characteristics.14

About the Votrient Patient Access Scheme

In order to make Votrient accessible to patients quickly, GSK has offered an innovative patient access scheme, which includes a straight 12.5% discount on the list price 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). The head-to-head study versus sunitinib (COMPARZ) is currently underway and is due to report in 2012.25 As advanced kidney cancer is one of the most difficult to treat malignancies and the side-effects of treatment can have a big impact on quality of life, having different treatment options available with different side-effect profiles allows patient and physician choice.5-10 Rather than wait until 2012 for the results of the head-to-head trial, GSK has proposed an innovative and flexible approach to pricing to enable patient and clinician choice, and access to pazopanib as soon as possible. GSK is confident that the evidence from this trial will demonstrate the full value of Votrient, but, if it does not, will pay a partial rebate to the NHS.

About renal cell carcinoma (RCC)

RCC accounts for over 80 per cent of kidney cancers in the UK.26 Worldwide and UK incidence, as well as mortality from RCC, is increasing.27 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.17

References

1) NICE. Pazopanib for the treatment of patients with advanced renal cell carcinoma. Final Appraisal Determination document. [insert URL when available] Accessed December 2010

2) Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma. NEJM. 2007; 356: 115-124

3) 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

4) 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

5) Hutson TE, Figlin RA, Kuhn JG et al. Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies. Oncologist 2008; 13: 1084-1096

6) Porta C, Szczylik C. Tolerability of first-line therapy for metastatic renal cell carcinoma. Cancer Treat Rev 2009; 35:297-307

7) Shepard DR, Garcia JA. Toxicity associated with the long-term use of targeted therapies in patients with advanced renal cell carcinoma. Expert Rev Anticancer Ther 2009; 9 (6): 795-805

8) Pyle L, Beirne D, Bird J et al. Managing the adverse events of sunitinib: a guide to empowering the patients. Cancer Nursing Practice 2008; 7: 42-46

9) Bird J, Hayter M. A review of the literature on the impact of renal cancer therapy on quality of life. J Clin Nurs 2009; 18: 2783-2800

10) Schwandt A, Wood LS, Rini B et al. Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma. OncoTargets and Therapy 2009; 2: 51-61

11) NICE. Sunitinib for the first-line treatment of advanced and/or metastatic renal cell carcinoma. NICE technology appraisal guidance 169. March 2009. http://www.nice.org.uk/nicemedia/live/12143/43556/43556.pdf Accessed December 2010

12) 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 [Epub ahead of print]

13) 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.

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

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

16) Cancer Research UK: Kidney cancer statistics UK. Available at: http://info.cancerresearchuk.org/cancerstats/types/kidney/ Accessed December 2010

17) Lam JS, Leppert JT, Belldegrum AS et al. Novel treatment approaches in the therapy of metastatic renal cell carcinoma. World J Urol 2005; 23: 202-212

18) Oudard S, George D, Medioni J et al. Treatment options in renal cell carcinoma: past, present and future. Ann Oncol 2007; 18 (suppl 10): x25-x31

19) Karaman MW, Herrgard S, Treiber DK et al. A quantitative analysis of kinase inhibitor selectivity. Nature Biotechnology 2008; 26: 127-13.

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

21) Votrientâ Summary Of Product Characteristics (SPC). GlaxoSmithKline, March 2010.

22) Hutson TE, Davis ID, Machiels J-PH et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol 2010; 28: 475-480

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

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

25) 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

26) Cancer Research UK: Types of kidney cancer. Available at: http://www.cancerhelp.org.uk/type/kidney-cancer/about/types-of-kidney-cancer Accessed December 2010

27) Cancer Research UK: Kidney cancer - UK incidence statistics. Available at: http://info.cancerresearchuk.org/cancerstats/types/kidney/incidence/. Accessed December 2010

Source:
GlaxoSmithKline

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