The UK National Institute for Health and Clinical Excellence (NICE), an independent organisation responsible for providing national (UK) guidance and standards on the promotion of good health and the prevention and treatment of ill health, has confirmed its decision not to approve cabazitaxel (Jevtana?;Black Triangle Drug; Sanofi) for use by the NHS. The decision followw an appeal from Sanofi and could effectively prevent thousands of men in the UK with advanced prostate cancer from accessing this life-extending treatment[1]. Today only 7 out of the 10 Cancer Drugs Funds in England offer unrestricted access to cabazitaxel and the devolved nations, Wales, Northern Ireland and Scotland have no similar fund in place.

Commenting on the guidance Sir Andrew Dillon, Chief Executive of NICE said: ?We need to be sure that new treatments provide sufficient benefits to patients to justify the significant resources the NHS would need to make available. Although cabazitaxel can extend life for some patients(The Committee concluded that cabazitaxel resulted in a mean improvement of greater than 3 months in mean overall survival), its price remains well above what the independent Committee appraising this drug considered acceptable, given the benefits it offers. Cabazitaxel is also associated with a number of side effects, and the Committee was concerned about the nature of the health-related quality of life information provided by the manufacturer.?

Concern
The most commonly occurring adverse reactions are related to bone marrow suppression which include anaemia, leukopenia, neutropenia, and thrombocytopenia and gastrointestinal events such as diarrhoea. For NICE, hamatological adverse events and diarrhoea were major concerns. The Committee noted that the incidence of neutropenia was lower among participants recruited at European centres than other centres. NICE was concerned that in TROPIC more participants in the cabazitaxel arm died from cardiac and renal complications than in the mitoxantrone arm.

Following consultation on the draft recommendations NICE considered three sources of data presented by the manufacturer (Sanofi), including the results of studies evaluating cardiac toxicity associated with cabazitaxel, the conclusions of a review by an expert panel of renal events observed with cabazitaxel, and post-marketing safety data. The reviewers concluded that there is no evidence of additional risk other than that included in the summary of product characteristics.

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Limited appeal
NICE received one appeal on its final draft guidance for this appraisal. The appeal was dismissed on all points. Reviewing the decision, Jasmin Hussein,M.D., Oncology Medical Manager, Sanofi UK, said: “Cabazitaxel offers an important new treatment option with significant clinical and improved quality of life benefits for men with advanced prostate cancer[1,2]. This decision by NICE is a major setback for these patients who have only a few treatment options.”

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Treatment option
Cabazitaxel is the first of recently licensed drugs for the treatment of metastatic hormone refractory prostate cancer (mHRPC) to significantly extend overall survival compared to mitoxantrone in men whose disease has progressed during or after treatment containing docetaxel (15.1 months median overall survival vs. 12.7 months in the control arm; HR=0.70 (95% CI; 0.59-0.83); P<0.0001)[1]. Men with this stage of cancer typically have a poor prognosis and until recently there have been no licensed treatments available to extend life[3]. Researchers and healthcare professionals treating patients with mHRPC feel that cabazitaxel represents a significant therapeutic advance in this regard.

The cost argument
Professor Jonathan Waxman, Imperial College London, noted: “This decision seeks to limit what we as clinicians can do for our patients and their families. The cost argument on which NICE bases their decision is false, giving a much higher estimate of true cost than applies in reality. As a result yet another successful and effective cancer treatment is denied our patients, a mortifying blow to cancer care in England. As the only route to access is now the Cancer Drugs Fund, a temporary arrangement that operates very differently around the country, I fear we’re heading towards a re-emergence of the postcode lottery.”

Decision on abiraterone
Prostate cancer patients, their families and charities are now waiting for NICE to issue their decision on abiraterone, another life-extending treatment, which is due imminently. In February 2012, NICE issued a negative draft decision for abiraterone as it was deemed the drug did not meet the end of life criteria for reimbursement.

“Cabazitaxel is one of only two licensed drugs available in the UK that offers the hope of precious extra time and quality of life benefits to men living with advanced prostate cancer. NICE’s decision not to recommend this drug means that men in England with advanced prostate cancer have to access it through the Cancer Drugs Fund. We know that there are inconsistencies across the country with how this fund is awarded which means some men will only be able to access one of these drugs in some areas. Men with advanced prostate cancer have so few treatment options available to them that they should be able to access both of these new treatments.” noted Emma Malcolm, Chief Executive, Prostate Action.

For more information:
[1] De Bono JS, Oudard S, Ozguroglu M et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castrate-resistant prostate cancer progressing after docetaxel treatment: A randomised open-label trial. Lancet 2010; 376: 1147-54
[2] Bahl A et al. Cabazitaxel for metastatic castrate-resistant prostate cancer(MCRPC): Interim safety and quality-of-life (QoL) data from the UK early access programme (NCT01254279), poster presented at the 2012 Genitourinary Cancers Symposium
[3] National Institute for Health and Clinical Excellence. Docetaxel for the treatment of hormone refractory metastatic prostate cancer. Technology Appraisal 101. London: NICE, 2006.

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