Unfair if rare: should the PBS change the way it lists cancer drugs?

The Pharmaceutical Benefits Scheme (PBS) spends over A$9 billion a year subsidising a wide range of drugs to ensure affordability for all Australians. But when it comes to rare cancers – such as bone and soft tissue tumours called sarcomas – the scheme falls short.

This happens for a number of reasons. The main one is that rarity means less value for money. But should our new understanding of how cancers develop and could be treated mean we should change the way the scheme registers cancer drugs?

Diagnosing cancers

Cancers used to be diagnosed by determining the organ, such as breast or lung, from which they came. Drugs were, and still are, registered by the Therapeutic Goods Administration (TGA) to use against these cancers if they are effective in clinical trials with acceptable side effects.

Because there are more patients for common cancer trials, and a larger market if the drugs are effective, more drugs to treat these are being tested and therefore registered. Rare cancers are those with an incidence of less than six cases for every 100,000 people. Their rarity means it’s not possible to do the gold standard large randomised controlled trials to determine efficacy.

The TGA refers to drugs used to treat rare diseases as orphan drugs and offers reduced application fees to register these. Despite this, there are still many small bowel cancers or neuroendocrine cancers for which potentially effective drugs are not registered.

Only once the TGA registers a drug for a particular cancer can an application be made for it to be subsidised on the PBS. Drugs are therefore more likely to be subsidised for common cancers, as the PBS evaluates whether the drug’s effectiveness warrants the price sought by the pharmaceutical developer.

But recently there has been a shift in how cancer researchers and doctors classify and treat cancers that could potentially influence the way drugs become registered.

From location to tumour type

Previously, chemotherapy drugs killed all dividing cells and relied on normal cells to repair themselves while the cancer cells died. Therapies are now being developed to specifically target the genetic makeup in each tumour - a wave of medicine referred to as “personalised”.

Other therapies – known as immunotherapies – target proteins that prevent the body’s immune cells from killing the cancer. The target proteins are found by looking at which genes in a particular cancer are altered (or mutated) to make the cells replicate and grow into unhealthy tumours.

So cancer treatment is becoming more dependent on the tumour’s genetic makeup rather than the organ of origin. Cancers at different locations, such as breast and prostate cancer for instance, may have identical targets that can respond to the same therapies. And cancers from the same organ can have different patterns of gene mutations, which means only those with the target may respond to specific drugs.

Drugs called PARP inhibitors, for instance, have been successful in breast cancers that carry the BRCA1 or BRCA2 gene mutations. These are being trialled in ovarian cancers with the same gene mutations.

Targeted therapies can be used to treat a rare cancer that shares the same mutations as a common cancer. The immunotherapy drug nivolumab, for instance, is successful in treating melanoma and lung cancer. And, as reported in ABC’s Australian Story program this week, it is being tried as a treatment for 36-year-old Danielle Tindle’s rare neuroendocrine tumour, which shares some characteristics with melanoma and lung cancers.

The issue is that targeted therapies are often coming onto the market at over A$100,000 for several months of treatment. And while nivolumab is subsidised to treat melanoma, a patient like Danielle has to pay full price, which is reportedly A$5,000 a shot.

Can we change the system?

To overcome this disparity, a specific fund could be established for rare cancers so they would not have to compete with more common cancers. Fees for TGA and PBS submissions would be set to encourage pharmaceutical companies to apply to register and list drugs for rare cancers.

Of course, the equity of that solution would depend on the size of the fund relative to need and whether the fund’s money was new or simply reduced the subsidy pool for more common cancers.

Another option is for the TGA to start registering targeted therapies on the basis of the target’s presence in the cancer, irrespective of the cancer’s organ of origin. The issue with this approach is that the evidence for efficacy would only be available from trials of more common cancers.

Also, although a targeted therapy isn’t effective in cancer that doesn’t have the target, the presence of the target doesn’t guarantee its effectiveness. This is because the tumour’s altered gene may not be responsible for driving the cancer’s growth, or may represent only one of the targets that need to be hit to stop it developing.

So limited trials that show efficacy of targeted therapies for rare cancers could lead to subsidising potentially ineffective drugs. A possible solution would be a risk-sharing model where, for example, a pharmaceutical company could fund initial courses of rare cancer drugs until there was enough evidence of efficacy, at which point the government subsidy would become available.

Such schemes have been used in France, Italy, Sweden, the United Kingdom and parts of the United States.

The challenge is to achieve a balance between allocating funding for the greatest good for the largest number of people, while also ensuring patients with rare cancers aren’t unfairly disadvantaged.