22 May 2013
When I first saw Stephanie* three years ago, she was newly diagnosed with chronic myeloid leukaemia (CML), a blood cancer that almost killed her just two weeks before.
At that time, the leukaemia had replaced the normal blood cells in her bone marrow, causing a life-threatening brain haemorrhage. Thankfully, we were able to control her bleeding, and had started Stephanie on a tyrosine kinase inhibitor (TKI), in the form of a daily pill.
The TKI attacks CML at its root cause, turning off a mutated protein that drives the growth of CML cells. In fact, she would probably live a normal lifespan and, if she wanted to, could get married, plan for a family and contribute to society — just as long as she kept taking the TKI. In fact, she might even outlive me, her middle-aged oncologist.
The success story of TKIs in CML has revolutionised cancer care in cancer clinics among first-world countries. TKIs have taught us that if we can identify the genetic mutations that cause a particular cancer and design therapies to target those mutations, there is a good chance that we will see both dramatic responses and increased survival compared to standard therapy.
In the pre-TKI era, less than 20 per cent of patients with CML survived 10 years, whereas now, we expect more than 80 per cent of patients to do so.
Cancer research, through collaborations with pharmaceutical companies, has effectively transformed CML from a deadly disease into a chronic illness, much like diabetes or hypertension.
A DIFFICULT PERSONAL CONVERSATION
Explaining her prognosis to Stephanie was easy, but then I had to counsel her about the practicalities of treatment. Side-effects are usually mild, and most patients are able to tolerate treatment well, even over decades.
More difficult was explaining that the TKI would cost over S$4,300 per month for the rest of her life. However, she could use S$1,200 a month from her Medisave account and, if she had basic MediShield, could deduct another S$1,200. That would still leave her to pay S$22,800 out of pocket for a year’s treatment.
Even if she had private insurance, many schemes would cap outpatient therapy at just a few months’ treatment every year.
Such daunting costs usually necessitate a difficult and challenging family conversation before the next appointment.
Stephanie and her family are not alone: Every year, 50 new CML patients and their families will have similar conversations.
A DIFFICULT NATIONAL CONVERSATION
Following close on the heels of TKIs, we have 39 United States Food and Drug Administration (FDA)-approved targeted cancer therapies directed against a wide variety of cancers.
However, not all the drugs are as dramatically successful as TKIs in CML.
Some targeted therapies only result in a survival increase of a few months or at most, a handful of years.
Despite their variable efficacy, almost all are expensive: Of the 12 cancer drugs approved by the FDA last year, 11 cost over US$100,000 (S$126,000) per year for US patients.
Faced with escalating medical costs, a well-informed public and a pipeline of expensive but increasingly effective life-prolonging therapies, a national conversation should take place.
Patients, patient advocates, government agencies, pharmaceutical companies, treating physicians as well as third-party payers all need to engage with each other to decide how society will support individuals like Stephanie.
This is a difficult conversation that needs to take place urgently since the stakes are so high.
Most of us know of at least one close friend or family member living with cancer and, increasingly, because of the success of cancer research, many have begun to appreciate the difference modern cancer therapy can make in extending survival and improving quality of life.
THE WAY AHEAD
We would not be the first country to have this conversation; others, such as the United Kingdom, have gone before us.
For CML and TKIs, decisions can be made on a rational, data-driven basis. We know how much the drugs cost, we know how many more years a CML patient on TKIs will live and, furthermore, we know the quality of life such individuals can expect to have.
Accordingly, we can calculate how much it costs to prolong survival by two or 10 years and, from a social welfare perspective, whether or not they are likely to continue contributing to society.
More difficult will be deciding what those additional years are worth.
Then again, in England, the National Institute for Health and Clinical Excellence values a year lived at around £30,000, or S$57,000, and recommends that its National Health Service supports TKI therapy for patients with CML.
[So what is the value of a life in Singapore? And how would we arrive at the number?]
An advantage of going through this process for CML is that it will then serve as a model for using transparent and data-based approaches to address similar situations in other cancers, or indeed other medical conditions, where expensive life-saving therapies are available.
HOW ELSE TO CONTROL COSTS?
Finally, and again taking a page from our experience in CML, discussions are under way between pharmaceutical companies and patients and their advocates about what constitutes a fair price for cancer drugs.
Such discussions will hopefully determine pricing that allows pharmaceutical companies to continue research into new drugs, but at the same time keep life-saving therapies within the reach of patients.
In the case of Glivec, the first TKI to be approved for CML, we also have numbers.
The cost of bringing a new cancer drug to patients is estimated at US$1 billion and, last year, revenues from Glivec were about US$4.7 billion. Should the drug, which cost about US$30,000 per year in 2001, continue to cost the same or even more (currently US$92,000 in the US)?
Additional research is important, even in CML. For example, we do not know why 20 per cent of CML patients fail to live as long as the lucky 80 per cent. Our team’s recent research showed that you were more likely to be in the 20 per cent if you inherited a specific mutation in the BIM gene found in 15 per cent of healthy East Asians.
However, while these unlucky individuals may not benefit as much from TKIs when given alone, we also found that a combination of a TKI and so-called “BH3-mimetic” drugs would overcome drug resistance.
Clinical trials are currently planned for this combination, and will hopefully allow us to maximise health care dollars for patients taking TKIs.
So, what happened at Stephanie’s next appointment? She found the resources to pay for the TKI, she did not have the BIM variant, and a generic TKI would soon be available. Perhaps she will outlive her oncologist, have peace of mind — and still be able to afford going to the movies.
* “Stephanie” is not an actual patient, but a composite of many patients.
[Unfortunate. Why was it necessary to "composite" a patient? For anonymity? Patience privacy/confidentiality? ]
ABOUT THE AUTHOR:
Dr Ong Sin Tiong is an Associate Professor in the Cancer and Stem Cell Biology Signature Research Programme at the Duke-NUS Graduate Medical School. He is also a clinician-scientist and medical oncologist, and Visiting Consultant at the Singapore General Hospital and National Cancer Centre Singapore. This article has input from colleagues, Drs David Matchar, Shirish Shenolikar, Charles Chuah and medical social worker Olivia Khoo.
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