Pierre-Fabre’s Javlor (vinflunine) has not been recommended for the treatment of advanced or metastatic transitional cell carcinoma of the urothelial tract by NICE in final guidance.

The bladder cancer drug was not recommended in final draft guidance published last year but manufacturer Pierre-Fabre submitted updated evidence to try and reverse that decision.

However, Sir Andrew Dillon, NICE Chief Executive, said the fresh evidence was inconclusive.

“The manufacturer has been unable to provide the Appraisal Committee with conclusive evidence on how effective vinflunine is, particularly the extent to which it can prolong survival compared with best supportive care,” he said.

“When we recommend the use of expensive treatments designed to extend life, we need to be confident about the nature and the extent of the benefit they bring.”

Despite the guidance, cancer patients currently receiving Javlor have the option to continue using the treatment until they and their clinicians consider it appropriate to stop.

National Cancer Director Mike Richards has outlined plans for a series of public awareness campaigns promoting early diagnosis of cancer.

The DH plans to repeat its national bowel cancer campaign, followed by local campaigns focused on ovarian cancer and ‘constellations’ of cancer symptoms.

Regional pilots are planned for campaigns around breast cancer in elderly women and renal/bladder cancer.

In a letter to NHS trust and PCT chief executives, Richards emphasises the importance of early diagnosis for improving cancer survival rates and notes the Government’s aim of saving 5,000 more lives per year by 2014/15.

The national bowel cancer awareness campaign that ran from January to March 2012 achieved a 50% increase in urgent GP referrals for suspected colorectal cancer in regions not involved in the pilot campaigns.

To build on this effect, the DH plans to repeat this campaign for four weeks from 28 August, using a range of advertising and community engagement strategies. It warns trusts that the campaign may increase pressure on secondary care facilities.

From January to mid-March 2013 the DH will test local campaigns on ovarian cancer and cancer symptom ‘constellations’, and will run regional pilots of campaigns on breast cancer in women over 70 and blood in urine (a potential symptom of renal or bladder cancer).

Hosted by regional Cancer Networks, the campaigns will form part of a national partnership programme to combine primary care and diagnostic services.

An innovative diabetes drug that the FDA declined to approve in January 2011 has been endorsed by the European Medicines Agency (EMA).

Forxiga (dapagliflozin), co-developed by AstraZeneca (AZ) and Bristol Myers-Squibb (BMS), is the first drug to treat type 2 diabetes by promoting excretion of sugar by the kidneys.

Concern over liver toxicity and cancer risks led the FDA to request more data on the drug, but the EMA determined that its benefits outweigh its risks.

Forxiga inhibits a target in the kidney known as SGLT2, blocking the absorption of blood glucose and causing its excretion in urine.

BMS, who discovered dapagliflozin, partnered with AZ in 2007 to develop the drug – which, if approved, would be the first SGLT2 inhibitor to reach the market.

However, in 2011 the FDA declined to give the drug marketing approval, citing evidence of increased rates of breast and bladder cancer and liver toxicity.

The agency requested further clinical data “to allow for a better assessment of the benefit-risk profile,” including results from ongoing studies and perhaps from new clinical trials.

The EMA said the increasing prevalence of type 2 diabetes and the side-effects of some current therapies meant there was a need for new treatment options.

According to the agency, clinical trials have shown that Forxiga improves blood glucose control either alone or in combination with other diabetes drugs, and its effect is sustained up to 102 weeks.

However, it noted, the increased risk of bladder and breast cancer was of concern, “especially in the light of potentially long treatment periods and a possible widespread use”.

The EMA said it will maintain “close observation” of these risks, following a planned study of the drug’s cardiovascular side-effects. It requested that the companies carry out an epidemiological study of Forxiga.

BMS Chief Executive Lamberto Andreotti said: “We are pleased the CHMP has given a positive assessment of the benefit/risk profile of this novel product in a new class for the treatment of type 2 diabetes, an area of high unmet medical need.”

The CHMP has confirmed that pioglitazone remains a valid second-line and third-line treatment option for certain patients with type 2 diabetes when others are not suitable or have failed to work.

The Committee reviewed the opinion given in July 2011 which clarified the treatments should remain as a treatment option despite a small increased risk of bladder cancer.

Doctors have now been “reminded” by the CHMP of the updated opinion, which has now been sent to the European Commission and is expected to be endorsed by the Standing Committee by the end of the year.

The Standing Committee on Medicinal Products for Human Use failed to endorse the initial opinion and called for another review in to the benefit-risk balance of pioglitazone-containing medicines.

The body, which consists of representatives of all EU Member States, has to be consulted before the European Commission transforms the EMA’s CHMP’s opinion into legally enforceable decisions.

A new fluorescent imaging agent to assist detection of papillary cancer of the bladder has been adopted by Thomas Jefferson University Hospital in the USA.

Cysview (known in Europe as Hexvix) is licensed by GE Healthcare from Norwegian company Photocure ASA.

Used with patients who are known or suspected to have bladder cancer, it guides blue light fluorescence cytoscopy (pictured), which highlights cancerous lesions in the bladder.

The use of Cysview for cytoscopy has been shown to improve surgical outcomes relative to standard white light cytoscopy alone.

Bladder cancer, most commonly caused by smoking, is the fourth most common type of cancer in men and the eighth most common in women.

“Bladder cancer is difficult to detect,” said Dr Leonard Gomella, Associate Director for Clinical Affairs at the Kimmel Cancer Center at Thomas Jefferson University Hospital. “A missed diagnosis can result in delayed or incomplete treatment, which may lead to serious complications and a lower chance of survival.

“Cysview represents an important advance in diagnostic technology, enabling more accurate diagnosis of bladder tumours compared to the standard technique. By facilitating early diagnosis of bladder cancer, this innovative imaging agent can enable appropriate, timely treatment that may improve patients’ chances of survival.”

Takeda and Eli Lilly are being sued by US-based litigation firm Girard Gibbs over the type 2 diabetes drug Actos (pioglitazone).

The lawsuit alleges that the two failed to warn consumers of the drug’s link to an increased risk of bladder cancer.

AJ De Bartolomeo, one of the main litigating lawyers, said manufacturers were required to issue warnings about the possible risks and negative side effects from their products.

Earlier this year in June, the FDA issued a safety alert in connection with the risk of bladder cancer with the prolonged usage of Actos.

“When a manufacturer decides not to provide full disclosure of the potential risks from a medication, doctors and patients cannot make informed decisions about what drug is right for them, and as a result, people suffer injuries unnecessarily,” Mr Bartolomeo said.

The EMA has confirmed anti-diabetic pioglitazone-containing medicines remain a valid option for certain patients with type 2 diabetes – despite a small increased risk of bladder cancer, following a review.

The results from various studies were reviewed and found a small increased risk for patients taking pioglitazone-containing medicines, particularly those using longer durations of higher cumulative doses.

However, the CHMP concluded the risk associated with the medicines can be reduced by appropriate patient selection and exclusion, and has not restricted the current indications of pioglitazone.

The formal review has been by the CHMP at the request of the European Commission.

As part of the assessment, the Committee considered advice from the EMA’s Scientific Advisory Group (SAG) on Diabetes/Endocrinology, and sourced data from preclinical studies, clinical studies, epidemiological studies and spontaneous reports.

Data from a meta-analysis of randomised controlled clinical studies found that 19 out of 12,506 patients taking pioglitazone had bladder cancer (0.15%) compared with 7 out of 10,212 patients not taking pioglitazone (0.07%).

Prescribers are now advised not to use the medicines in patients with current or who have a history of bladder cancer, or in patients with un-investigated macroscopic haematuria

Despite the decision, the CHMP has agreed there is a need for further analysis of the types, evolution and severity of bladder cancer in patients treated with pioglitazone compared to diabetics not treated with pioglitazone.

It has now asked Takeda, the marketing authorisation holder, to conduct a pan-European epidemiological study focusing on more robust characterisation of the risk, in particular the risk period and risk with increasing age, to inform the evidence-base for risk minimisation measures.

Actos, Glustin, Competact, Glubrava and Tandemact are all pioglitazone-containing medicines authorised in the EU.

The CHMP will delay its decision on the future of pioglitazone-containing medicines until July.

Reviews are on-going into the results from several studies to assess the occurrence of bladder cancer, and to assess their impact on the balance of the benefits and risks of the medicines.

The Committee says at this stage there are still “numerous issues” that need to be resolved before it can make a final recommendation.

Pioglitazone-containing medicines include Actos, Glustin, Competact, Glubrava and Tandemact.

The link between bladder cancer in association with pioglitazone has been under review for more than a decade by the CHMP since it was first granted marketing authorisation.

The current review of pioglitazone-containing medicines was initiated in March at the request of the European Commission, following an increased number of spontaneous reports of bladder cancer.

Since then pharmacoepidemiological studies, non-clinical and clinical data and post-marketing reports are all being conducted by the EMA.

Takeda, the marketing authorisation holder, is also conducting a series of post-authorisation studies aimed at identifying incident malignancies associated with pioglitazone treatment in a cohort of diabetic patients.

Three interim studies by Takeda have not yet confirmed a clear association, but signal a potential increased risk in those with the longest exposure and highest cumulative dose.

The CHMP says that the accumulated evidence provided by additionally preclinical studies, epidemiological data and the PROactive trial (a placebo-controlled clinical trial) taken in its totality, represents a clinically relevant signal which requires further evaluation.

At the CHMP’s June meeting, the results of a retrospective cohort study carried out in France were discussed. The Committee considered that the study strengthened the signal of a small increased risk of bladder cancer. But it was also found that the study had several methodological limitations which limit the strength of evidence.

The Scientific Advisory Group on Diabetes/Endocrinology (SAG-D/E) has now been asked to discuss the place of pioglitazone-containing medicines for the treatment of diabetes and the clinical relevance of the available data on any cancer risk, and to identify risk-minimisation measures for patients in clinical practice.

Recommendations of the SAG-D/E will be analysed and discussed at the CHMP’s next meeting in July, where a final option on the benefits and risks of these medicines will be made.

NICE has failed to recommend bladder cancer treatment Javlor (vinflunine) in preliminary draft guidance.

The Institute said the treatment is too expensive for the NHS and that manufacturer Pierre-Fabre had failed to supply suitable evidence of its clinical effectiveness.

Sir Andrew Dillon, NICE Chief Executive, said that although there is data which indicates Javlor extends life, there is ‘considerable uncertainty’ around the details provided by the French company.

Javlor is used to treat metastatic transitional cell carcinoma of the urothelial tract which has progressed following prior treatment with platinum-containing chemotherapy.

During the appraisal NICE requested a comparative study with similar treatments to establish its effectiveness.

“The study compared vinflunine to best supportive care,” Sir Andrew Dillon said, “however it failed to provide the committee with conclusive evidence about the clinical effectiveness of vinflunine, particularly the extent to which it survival is prolonged compared with best supportive care.

“Although there is some evidence to indicate that vinflunine can extend life for patients with transitional cell carcinoma, there is considerable uncertainty around the estimates provided by the manufacturer.”

NICE also revealed that the estimated cost per quality adjusted life year gained is in excess of £120,000, well above any other treatment it has previously accepted as cost effective. Concerns were also raised by the Appraisal Committee that the adverse effects of Javlor, which includes severe constipation, were not taken into account in the economic evaluation.