First tarceva Now ALIMTA!!!!!!!!!!!!

[RandyW]

Victory for cancer drug campaign

Jan 24 2008 by Audrey Barton, The Journal

NORTH-EAST campaigners have won their three-year battle to get a life-prolonging lung cancer drug funded on the NHS.

Alimta, which is the only treatment for asbestos-related cancer mesothelioma, will be given to NHS patients with advanced stages of the disease who cannot have surgery.

The National Institute for Health and Clinical Excellence (NICE) yesterday issued guidance following a two-and-a-half year approval process, which included two appeals.

The guidance means that primary care trusts (PCTs) will be able to fund the drug for all NHS patients with mesothelioma for whom the treatment is suitable.

The North-East has one of the highest concentrations of the disease which has its roots in heavy industry such as shipbuilding.

Chris Knighton, of Wallsend, North Tyneside, lost her husband Mick to mesothelioma, prompting her to raise more than £330,000 for research.

The founder of the Mick Knighton Mesothelioma Research Fund said: “I am absolutely delighted as really today is a victory for us as we have been fighting for this for three years.

“I think that hopefully in the future making the drug accessible to patients who have had surgery is something that could be possibly looked at to make it accessible for more patients. My concern is that now PCTs make the drug available for mesothelioma patients as they don’t have the benefit of time.”

Arthur Tiffin, 53, of North Walbottle, Newcastle, who died from mesothelioma last summer, led the campaign to make Alimta available for patients in the region which was successful in 2005. NICE initially ruled against the use of Alimta across the NHS but made a U-turn last year and issued guidance recommending the life prolonging drug.

But two appeals were lodged in September, the first for the drug to be extended for people who had surgery, and the second stating that it did not fall within the special criteria for funding drugs over a £30,000 threshold have been dismissed on all counts. Yesterday’s recommendation was delayed by several months subject to an appeal hearing but marks the end of a long running battle for the drug to be funded on the NHS.

Blaydon MP Dave Anderson, a patron of the Mick Knighton Mesothelioma Research Fund charity, said: “The Government now needs to ensure that there is a level playing field across the whole of the UK for workers stricken by this disease.

“It is only right that treatment is available according to need and not cost.

“However, the delay getting this decision has added to the mental and physical anguish for sufferers and has sadly come too late for some.”

He is calling on PCTs to immediately fund the treatment and not wait until the end of the three month implementation period.

For previous Alimta stories from The Journal click the links below

Patient in legal battle to get cancer drug

Cancer drug battle doctor to campaign

Cancer patients' glimmer of hope

Outcry at delay in decision on cancer drug

[gpawelski]

Tarceva is a "targeted" therapy, in that it halts the growth of certain cancers by zeroing in on a signaling molecule critical to the survival of those cancer cells. The drug is effective in about 10-15% of patients with non-small cell lung cancer. The drug works specifically in patients whose cancers contain mutations in a gene that encodes the epidermal growth factor receptor (EGFR). Lung cancer patients with these mutations are often people who have never smoked.

Although this targeted therapy is initially effective in this subset of patients, the drug eventually stops working, and the tumor begins to grow again. This is called acquired or secondary resistance. This is different from primary resistance, which means that the drugs never work at all. The change of a single base in DNA that encodes the mutant EGFR protein has been shown to cause drug resistance. The story is the same as for Erbitux and Iressa. Drug resistance evolves by multiple mechanisms.

Initially, tumors have the kinds of mutations in the EGFR gene that were previously associated with responsiveness to these drugs. But, sometime tumors grow despite continued therapy because an additional mutation in the EGFR gene, strongly implies that the second mutation was the cause of drug resistance. Biochemical studies have shown that this second EGFR mutation, which was the same as before, could confer resistance to the EGFR mutants normally sensitive to these drugs.

It is especially interesting to note that the mutation is strictly analogous to a mutation that can make it tumor resistant. Non-small cell lung cancer makes up about 80 percent of all lung cancers. Mutations in a gene called KRAS, which encodes a signaling protein activated by EGFR, are found in 15 to 30 percent of these cancers. The presence of a mutated KRAS gene in a biopsy sample is associated with primary resistance to these drugs.

Tumor cells from patients in a study who developed secondary resistance to Tarceva after an initial response on therapy did not have mutations in KRAS. Rather, these tumor cells had new mutations in EGFR. This further indicates that secondary resistance is very different from primary resistance.

All the EGFR mutation or amplification studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if Tarceva is better or worse than some other drug which may target this. There are differences. The drug has to get inside the cells in order to target anything.

EGF-targeted drugs like Tarceva are poorly-predicted by measuring the ostansible target EGFR, but can be well-predicted by measuring the effect of the drug on the "function" of live cells. An EGFRx targeted therapy profile includes analysis of the following targeted drugs: Tarceva, Iressa, Nexavar, and Sutent.

Literature Citation:

PLoS Medicine, February 22, 2005

Eur J Clin Invest 37 (suppl. 1):60, 2007

Alimta (pemetrexed) is a very promising drug. It is considered to be a significant advance than other available treatments. Toxicity is relatively low. It is not a "me too" drug, but is actually a third generation drug of its kind. Studies have shown that Alimta improves survival, albeit modestly, compared with supportive care only. Expense is horrendous though. If you fit into the subset of patients that this drug works well with, I'm sure it will work well.