Extending survival: powerful late-stage melanoma treatment to be considered for PBS

Dr Georgina Long

'A massive step forward' in melanoma treatment

About a quarter of an hour into our interview, Dr Georgina Long - a medical researcher at the Melanoma Institute Australia - takes a phone call. We're sitting in a pair of leather couches in a smallish meeting room, where Long has been talking intensely about a series of clinical trials the Institute has been running. The trials focus on medications like Vemurafenib, a new type of anti-cancer drug called a BRAF inhibitor. She gets up and moves to the far side of the room. I listen intently, while pretending to glance over my notes.

From the half of the conversation I can hear, the caller is trying to get a patient onto her trial. Long's voice is sympathetic. You can hear that the conversation has a sense of urgency about it. When she hangs up, Long stops pacing and sits back down on the edge of the couch. I ask about the caller. She tells me it was a doctor, who just diagnosed a patient with a melanoma metastasis.

Even a few years ago, the patient's remaining lifespan would have been measured in months, with little hope of reprieve. With BRAF inhibitor drugs like Vemurafenib, that prognosis has a chance of being spectacularly different.

'It's been a desert in melanoma for many, many years,' Long says. 'Negative clinical trial after negative clinical trial. Nothing worked with melanoma. This is a massive step forward.'

The hunt for mutants

Zelboraf is the product name of the drug Vemurafenib. It's one of a new class of drugs called BRAF  (pronounced "bee-raff") inhibitors.

BRAF inhibitors take advantage of the fact that metastatic melanomas - melanomas that have spread from their primary site to other organs like the brain, lungs, abdomen - often carry a mutation to an gene called BRAF. In normal body cells, the BRAF gene is a factory for making BRAF protein, an important element in the cell lifecycle. In melanomas, about 40% - 60% of patients will have the mutant version of the BRAF protein. And this is where BRAF inhibitor drugs come in.

To drug-makers, the BRAF mutation is a bit like having the cancer cells don a giant target. 'With Vemurafenib', says Long, 'we can inhibit the abnormal, mutated protein. The normal BRAF protein in [non-melanoma] cells is unaffected. Vemurafenib binds the mutated protein and stops it from signalling to the cell to divide and proliferate.' Effectively, it stops the cancer cells in their tracks, and actually shrinks melanoma tumours.

Long is quick to point out that the drug - a product pioneered by pharmaceutical companies Roche and Plexxikon - is a not a cure for metastatic melanoma. That said, its effect is impressive, to say the least. 'Prior to 2009, if a patient walked through my door with metastatic melanoma, they would survive on average a median 9 months,' Long says intently. 'In the phase two study of Vemurafenib, in patients who had already had other treatment, and then were given Vemurafenib second line, the median survival is 15.9 months from time of starting Vemurafenib.'

Extending quality of life, not just the fact of being alive

'He was an older guy,' says Long. 'A marathon runner, won prizes, very fit.' She is talking about a patient who took part in one of her earlier clinical trials. Towards the end of 2009, before commencing on the BRAF inhibitor, he had melanoma metastases throughout his body, and was going downhill quickly. 'He'd lost kilograms of weight, he wasn't eating. He'd stopped running and going outdoors. He was on morphine because of the pain. He had a lot of melanoma that was sitting under the skin of his back - very painful. Lung metastases, abdominal metastases...'

In the patient's own words, 'I was on my knees'.

Then he started the Vemurafenib treatment. Within 48 hours, he was eating full meals. He felt fantastic. 'It was like a switch,' Long remembers. 'Within six days, there was a dramatic response. By day 42, [the melanoma metastases] had almost completely disappeared.'

So what does someone do when they were about to die, and suddenly, unexpectedly, they find themselves with a healthy, productive reprieve?

'He wrote a book,' says Long. 'He got his affairs in order. He got his wedding album done that he'd been meaning to do for 50 years. He saw the birth of his great grandchild. He has died since, but he had 18 months that he never expected - 18 months of useful, high-quality living.'

Getting Venurafnib on the PBS

Vemurafenib (Zelboraf) is being considered for inclusion on the Pharmaceutical Benefits Scheme. The Government will be making the call in November this year. It's a decision that has to take into account a range of factors. The drug would be a relatively expensive addition to the taxpayer funded scheme. But the case for adding it is compelling; the benefits go beyond just kindness - although kindness must be a consideration too. The drug - indeed, that class of drugs - extends not just lifespan, but productive, high-quality lifespan. Plus, the BRAF mutation that makes it effective is more common in younger melanoma patients. And in Australia, that's very significant.

Melanoma is Australia's cancer. It has the horrifying distinction of being a cancer that appears not just in older demographics, but in the young. Long tells of a 23 year old PhD student, who was slammed with a diagnosis of metastatic melanoma. 'She had three weeks to live when I started her on a BRAF inhibitor,' says Long. 'It takes time to respond, and she just deteriorated in front of my eyes. In the last week, she was bed bound.'

Then the drug began to work. 'She walks out of hospital, goes back to full-time study, she does another year of her PhD. She writes two papers- and she dies subsequently, but, it's not a year of being attached to chemo. It's a tablet. It's a year of productive life in a young, young person.'

And that's the amazing thing about Vemrafenib, and other drugs in its class. Unlike chemotherapy, the treatment is simple, effective, and allows people to get on with their lives. There's the story of a 50 year old - still alive after three years of treatment, who works, surfs, and helps out at his beach club. He has access to the drug because he is part of the trial; but under ordinary circumstances, the drug would cost thousands of dollars per month. In a scenario without PBS subsidisation, it is unlikely he would be here today.

The future of melanoma treatment

Long and her colleagues, who range from scientists to surgeons, nurses, trial coordinators and others, work in clinical translational research. She describes it as research that goes 'from the bed to the bench and then back to the bed'. The model is geared towards getting results quickly for people with cancer, people who may not have much time. With the success of the Vemurafenib trials, Long and the Melanoma Institute Australia are looking at ways of extending the drug's durability, and halting disease progression for longer and longer periods.

This includes combining the drug with other pharmaceuticals that harness the power of the immune system to incite one's body into fighting melanoma tumours, destroying cells that may otherwise not respond to the Vemurafenib treatment alone.

So is there a potential a cure here for metastatic melanoma? Not yet, but maybe in the future - at least for melanomas that have a BRAF mutation. For Long, the cure is about more than molecular science, and mortality statistics. The bed-to-bench-to-bed approach that the Institute takes means that she has direct, close involvement with the people she is trying to help. 'I think about people I know,' she says to me, 'and it inspires me to do better.'

For more information about Vemurafenib, visit the Melanoma Institute Australia's website. You can also donate to the Melanoma Institute Australia.

Post a comment


23:01, 4 September 2012 | Author : Courtney

that if my mother had the mutoitan gene for the braf, he would give her the drug. However, in the meantime, her result was positive for the braf mutoitan gene. my mothers consultant has said now that my mother will not receive the drug and she is palliative. my mother is fully corpus mentus and of course is astounded as much as we are. he said that patients have became very toxic to this drug. eventhough, when i did alot of research into its success it was very positive. can you please advise me. we are now willing to pay for the drug as a family. any suggestions.

22:53, 24 July 2012 | Author : Peter W

I have a friend who had stage II melanoma. I wander if this could help with early stage melanoma too?

9:18, 24 July 2012 | Author : Dianne Henley

Every little step forward can lead to a cure. I have melanoma metastis which is non BRAF. This drug gives hope to those who are diagnosed in this catergory. With my mother dying last year from this cruel cancer, I can only hope that my sisters, my children, and grandchildren dont suffer the same fate.Thank goodness we have so much research in this area and a miracle that leads to a cure would be great!

23:41, 23 July 2012 | Author : Pensandfeathers

Are ther any clinical trials in New Zealand?

15:10, 23 July 2012 | Author : CitizenKate

This is quite amazing. It's a whole new way of fighting cancer. Nice interview btw.

12.40, 23 July 2012 | Author : Dee

Congratulations on these trials. It's exciting to see the advancements & opportunities that are being given to Pt's who would otherwise be left with no hope & certainly no quality of life.

My husband was diagnosed with Stage III Melanoma about 6 yrs ago & participated in a trial (not this one though). I'm pleased to say he's currently in remission, but we have over these yrs made & lost friends with Melanoma who had very poor quality of life depending on what treatment plans were offered to them.

Trials are the ONLY way to find the advancements & potentially a cure for Melanoma. Please support Melanoma Institute Australia in whichever way you can.

I pray that our Government will see sense in regards to PBS for this drug since they overlooked Yervoy a few months ago.

Dee :-D

10:01, 23 July 2012 | Author : Danielle

Thank you for writing this article about this exciting new therapy. Although it is not a cure, this new wave of therapy offers real hope to patients who previously had none.

Although some will argue that this shouldn't be on the PBS because it only buys people a few months life extension, that is such a precious gift that we simply cannot deny people. These people simply have no other options. In a disease that hits people in the prime of their lives, a few extra months of life - and productive life, at that - can mean that a young man will see his baby born, or a student can graduate from university. What right do we have to deny them access to this treatment?

9:22, 22 July 2012 | Author : navelgazeteer

@savvy-bee We're well away from a cure - for AIDS or melanoma. Not that these advances aren't amazing, but every step takes time and some of them will always lead to dead ends. Time will tell.

20:12, 21 July 2012 | Author : Savvy-bee

Its amazing what medicine can do nowadays. We're almost curing AIDS, almost curing own family has had a history of cancers. I just wish they had been diagnosed in a time where medical advances could have spared them so much suffering.

12:45, 21 July 2012 | Author : JayH

The article doesn't mention that BRAF inhibitors can be used for other cancers too (e.g. potentially colon/rectal).