'I don't want to die, I still have things to do': Keytruda wins Ron Walker's war on cancer

Christmas 2012 was meant to be Ron Walker's last. Rather than accept defeat, the prominent businessman flew to the US to join the trial of a drug that has cleared him of cancer. Now he is hell-bent on making that drug available in Australia.

Holograms of Ron Walker's body spin on the computer screen inside a small office at the Peter MacCallum Cancer Centre in Melbourne. Professor Rod Hicks, director of cancer imaging, is sitting in front of a glowing screen. He points to the first image and its exquisite, three-dimensional detail. "I call this the dead man walking scan. It's incompatible with ongoing existence."

Ron Walker is determined to bring the drug he says freed him from caner to Australia.Credit: Josh Robenstone

Walker's towering six foot six (1.98m) frame has been shrunk to the small holographic image on the computer screen and it is covered in red dots. The image is dated November 2012 and it was created from technology that overlays CT and PET scans of Walker's body. Three months earlier a similar image had revealed only a few red dots. The dots typically mark where cancer was growing inside Walker's body and it was everywhere. Six tumours were clustered in his brain. The cancer had colonised his lungs, reducing his breathing. Eventually those tumours would suffocate him if the pressure from the growing brain tumours didn't force him into unconsciousness and kill him first. The cancer was also in Walker's bones and his left adrenal gland was no longer gland but cancer instead. The picture Hicks is looking at is a portrait of a dying man.

Walker, one of Australia's wealthiest and most successful businessmen, had been told to go home, get his affairs in order and inform his wife Barbara, three children and three grandchildren that he had only a few months to live.

Professor Grant McArthur at the Peter MacCallum Cancer Centre in Melbourne.Credit: Josh Robenstone

Back at the glowing computer screen Professor Hicks shifts his finger slowly to a second image. It's late 2014 as we sit in his office, and it's as if Hicks still can't believe the image before him, which was made that October. "The drug has had quite a miraculous effect," says Hicks. "It's become the paradigm of hope for a whole lot of cancers."

There is no cancer on Walker's latest body scan. It's incredible. Ron Walker is clear of the insidious disease that had been growing, spreading and killing him. "I'm the luckiest guy alive," says Walker, 75, who has been sitting near Hicks, and is dressed in a smart navy suit, blue tie, cream business shirt and matching pocket handkerchief. He's been watching the computer screen and the holograms of himself spin around. There's the dead Walker. There's the living Walker. He still marvels at those images, and at the description of the earlier image as the dead man walking scan. "I knew, when he said that to me, what I was in for," recalls Walker. "I didn't want to die. I had things to do." As he sits there, he looks like a man who has had death inside him, clawing at him. He still hasn't regained his strength and is battle weary from fighting the cancer. The interview is a strain but he has an important story to tell and it's about a breakthrough cancer drug called Keytruda. "Every day I wake up I know I'm just a lucky person and that's why I will continue to make sure others will be as lucky as I am now," he says.

Walker's journey towards finding Keytruda began in February 2012 when he first noticed a shiny translucent corn on his forehead, just beneath where his still ginger hair falls. Fastidious about his health in his older years, he had it removed and sent for testing. The test came back: it was a melanoma, the deadliest of skin cancers.

The melanoma may have had its roots in the folly of Walker's youth. The fair-skinned young man of the 1950s lathered on baby oil and sunbaked with his friends on the popular surf beaches of Victoria's Torquay. They would lie there frying beneath the sun trying to meet and impress girls. Walker notes wryly it was do that or "otherwise lead a life of isolation".

It was not manly in the 1950s to wear a hat and there was no slip, slop, slap sun safety campaign. Rather, in that era tanned skin was considered healthy and soaking up the sun was encouraged. The young Walker would often travel home in agony at the end of the day on the beach, blisters rising on his back from the sunburn. "I had to stay off the beach until the blisters went down," he remembers.

In the decades to come, Walker would transform himself from sun worshipper to property developer, building a $795 million fortune. He jointly managed Hudson Conway, which built Melbourne's Crown Casino, and later co-owned property developer Evolve Development. Walker also had significant other roles in his long and illustrious career. These included Lord Mayor of Melbourne, treasurer of the federal Liberal Party, overseas treasurer for the British Conservative Party, a director of Crown and chairman of Fairfax Media, publisher of the AFR Magazine. He was about to add cancer victim to his résumé.

Red dot warnings

After the melanoma was diagnosed a biopsy of the nearest lymph node was done to determine if the cancer had spread. The result was negative and so Walker, who was still a director of Evolve and chairman of the Australian Grand Prix Corporation, returned to work. But the cancer had fooled the doctors. Bypassing the obvious nearest lymph node, which doctors routinely check to rule out the spread of such cancer, the cancerous cells had chosen a different path. Cancer cells travel via lymphatic or blood vessels along the body. To get to Walker's brain, the cancer cells went via the blood vessels. Most cancers, once they spread, are incurable.

Walker first began to worry something might be wrong in late April when some minor abnormalities appeared in a blood test for cholesterol, two months after he had been given the all clear. Further testing through May and June confirmed his worst fears. It was cancer. The first image made by Hicks's team in June displayed the red dots. Walker had faced cancer before but only on behalf of loved ones. His mother and wife had both had breast cancer.

The diagnosis hit Walker like a one-two punch but he refused to show it. He had no time for self-pity. "Never once did I say, why me?" Possibly because he knew the futility of the question and that the simple answer would have been, "Why not?" Cancer doesn't discriminate. Walker's physician, Dr Anne-Marie Pellizzer, had the task of breaking the bad news. "Ron was very professional about it," she says. "He was very matter of fact, 'OK, what do we do next?' He told his personal assistant Daniele to clear the diary and he made it his number one priority, which is how he approached it the whole time.

"I deal with some rich and famous people and a lot of them don't make it their priority and often push it to one side or are in denial; what they don't realise is if you don't get your health right the rest doesn't matter," says Pellizzer, who has known Walker since 2010 when he fell off his bicycle riding around Melbourne's Royal Botanic Gardens – he hit his head and a blood clot formed, which later required surgery.

After learning he had cancer, Walker set out with a single-minded belief he could beat it. "I was focused the whole time that I could beat this terrible disease. I didn't want to start planning for the future in the case of death. All I wanted to focus on was living." From June, Walker and his oncologist Professor Grant McArthur, co-head of Cancer Therapeutics at the Peter MacCallum Cancer Centre, prepared his treatment. What followed would be a harrowing few months for Walker. In July, he would undergo radiation treatment on his adrenal gland, which had grown to the size of a tennis ball when it's usually a bit smaller than a matchbox. In August, he would receive an infusion of an immunotherapy drug called Yervoy, which is given to melanoma patients who typically can't be treated with surgery. It would have almost fatal results.

Yervoy is one of a promising new crop of immunotherapy drugs that use the patient's own immune system to fight cancer, and has been found to be most effective in melanoma patients. It blocks a molecule called CTLA-4, which normally helps keep in check the immune system cells, called T-cells. When Yervoy blocks CTLA-4, the drug takes the brake off the immune system and allows the T-cells to activate and proliferate to attack the cancer cells. McArthur says Yervoy has about a 20 per cent success rate in patients and it can have side effects.

In Walker's case the side effect was a severe autoimmune disorder. Because Yervoy revs up the T-cells, the drug can cause a powerful autoimmune reaction where the immune system attacks normal cells in the body. Walker's immune system began attacking his stomach wall, almost causing it to rupture. "It nearly killed me," he says. After such a reaction to Yervoy it was impossible for Walker to continue on the drug.

"Because I had this violent reaction in my body I was able to move on and search for another drug," he says, seeing a silver lining. Nonetheless, it was a low point for Walker. He recalls a visit he had from his close friend Jeff Kennett, the former Victorian premier, at the time. "Jeff Kennett came in and sat on my bed and said, 'You look like shit'."

By November 2012, scans produced an image that read like a death sentence. "I was told to get my affairs in order because I wouldn't live until next Christmas," says Walker. But he was still willing to wager there was another drug out there he hadn't tried. "It was a case of battling the odds and getting the right technology to fix me up."

McArthur had told him there was another drug, Keytruda, and the early clinical data of its use in melanoma patients was very promising. There were phase 1 clinical trials of Keytruda in Australia but they were full. If Walker wanted to try the drug he would have to go overseas and there was no guarantee, even then, that he would get a spot.

"It's difficult to advise people to consider looking for clinical trials outside of their home town," says McArthur. "It's a very hard thing for a patient to get on a plane and be commuting backwards and forwards and not very many will take that up. Most treatments I have seen come through I have not advised people to do that. The early data would have to be very exciting to justify doing that and it was with Keytruda."

Please keep the hair

For Walker it was quite simply a race against time. "I knew time was running out and I had to make the connection pretty quick. The melanoma had expanded and I was in deep trouble. It was a dash to the finish line as far as I was concerned."

Walker was sent for brain radiation in November. Radiation uses beams of intense energy to try to kill cancer cells by damaging their DNA. "I made it clear I did not want to lose my hair," says Walker, laughing at his own vanity when he was fighting for his life. Walker had always had a handsome head of hair but the risk with radiation was it might never grow back. "They said: 'We'll do a deal with you. We'll keep your eyebrows but your hair will be gone'."

His lack of hair was apparent three months later in February 2013, when Walker made a rare public appearance at an event for the Australian Grand Prix. "I made a mistake," says Walker of going to the event where he would make headlines. The then-premier, Ted Baillieu, drew attention to Walker and his ill health, saying: "Thank you for everything you have done for major events in this city. It's fantastic to see you here. I know you have not been feeling fantastic lately, but I hope this helps to cheer you up." After Baillieu's kind words all eyes and cameras turned to Walker. He still cringes as he remembers the moment. "The whole media pack turned to me and then I was in The Age, which showed me as bald as a badger. It looked shocking."

Keytruda is an immunotherapy drug, like Yervoy, which co-opts the body's immune system into recognising, attacking and destroying cancer cells. It acts in a different way to Yervoy; Keytruda blocks a molecule called PD-1. "The cancer is very clever. It puts out this molecule PD-1 and turns off the body's immune response so it can survive and stop the immune system from attacking it," says McArthur. Keytruda specifically disrupts that molecular interaction. "We still have to stop and take a breath at how it could be this relatively simple," says McArthur. "We are very surprised. This is the biggest breakthrough we've had."

Some researchers say that blocking PD-1 triggers an immune response more targeted to the cancer than Yervoy. The latter works earlier on in the immune-cell activation process and the concern is that because of this it may cause more damage to normal tissue. Trials comparing Yervoy and Keytruda are ongoing. McArthur says his best estimate of the potential success rate of Keytruda, based on available data, "is going to be in the order of 40 per cent".

So far, Keytruda has been most effective treating melanoma and certain lung cancers but it is being trialled in about 30 cancers, such as breast, bladder and gastric, on more than 6000 patients globally. McArthur says science needs to further understand why some cancers respond better to Keytruda than others. "One of the strong hypotheses is that the cancers that are the most mutated and have the most damage to their DNA are the ones that respond the best. This is really very interesting science because melanoma and lung cancer are caused by UV radiation and tobacco and are the most mutated cancers we see." Still, McArthur says such immunotherapy drugs are a foot in the door to fighting other cancers. "Yes this is great for melanoma but now this mechanism has unlocked new approaches for many cancers. It's going to completely change the way we treat cancer."

Keytruda has been in phase 1 trials since 2011 globally, including in Australia. Phase 1 trials are the very first tests of a new drug in humans to determine dosage, safety and side effects. Such studies are typically done in a small group of patients. However, Keytruda's initial trial grew to more than 1000 patients with various types of cancer and is understood to have been one of the biggest phase 1 cancer studies ever. Typically a drug goes through three phases of clinical trials to show it can prolong life before it's approved and gets to market. Keytruda's phase 1 results were so compelling in melanoma and other cancer patients, it was given breakthrough therapy designation by the US Food and Drug Administration (FDA) and accelerated to the market for use in melanoma patients in September 2014. The basis for this was that it offered a substantial improvement on treatments already available. Shortly after this the FDA also approved it for use in certain lung cancer patients.

Keytruda is made by pharmaceutical giant Merck, known as MSD outside North America. Its rival, Bristol-Myers Squibb, which makes Yervoy, is trialling a similar drug to Keytruda, called Opdivo, which has been approved in the US and Japan. McArthur says the immunotherapy drugs are the biggest leap in treating cancer in his three decades in medicine. "If 10 years ago you asked me would we get treatments that are putting 20 to 40 per cent of patients with melanoma into long-term remission and potentially curing them, I would have said no. Now we are seeing that. I'm very hopeful that there will be patients with advanced melanoma that we will be effectively curing as a result of these treatments."

Keytruda has enabled patients of McArthur's in their 30s and 40s, who were critically ill, to return to work. He says this introduces a whole new dimension into the debate about the cost effectiveness of such drugs given the economic benefit they deliver in allowing individuals to return to work; reducing the need for family or friends to act as carers, or the drain on the healthcare system. "It's a major game changer," he says.

For Walker, however, such words were little more than a pipedream when he began his search for a trial in late 2012. McArthur asked his network of oncologist peers for help. Clinical trial slots were available at the University of California's Ronald Reagan Medical Center in Los Angeles, which were being overseen by Professor Antoni Ribas. But Walker would only be accepted if doctors there assessed him as a suitable candidate. If his cancer tumours were growing aggressively he would not be eligible. They had to be stable.

Meanwhile, Walker was leaving nothing to chance. He called "anyone who knew anyone at the FDA" who might be able to lobby to get him on the program. He rang Andrew Peacock, a friend and former Liberal Party leader and ambassador to Washington, who was living in Texas. Walker says about the only number he didn't call was former US Secretary of State Hillary Clinton's, opting against ringing her when he learned she'd had a fall. When it came to others, he didn't hold back. "I sent a copy of the things I had done to try and impress people I was a willing and able candidate for this drug."

In January 2013 Walker travelled to LA to meet Ribas. "I put my best foot forward the day I first went to the hospital," says Walker. "I wanted them to love me. I had interview after interview with scientists. I wanted them to know that they were backing the right horse." He was deemed eligible for the trial. McArthur stresses Walker was not selected because of who he is in Australia. "Some people say he got on to the trial because he's Ron Walker. That's not the case at all. Ron got lucky because there were slots available on the first clinical trial of Keytruda in the US but not in Australia. Ron had the means to be able to travel to LA, but it could have been anyone who got that spot."

During his second visit to LA, in late January, Walker received his first infusion of Keytruda. From the outset of his diagnosis, Walker had approached his fight against cancer as a business project. He wasn't about to shed his persona just because he was dying and would arrive for treatments wearing a suit when patients around him were dressed in tracksuit pants and casual wear. And he made a key appointment to help shorten the odds. Walker says he was too ill to manage his medical affairs and he wanted all the information handled by one trained and experienced person who would stay on top of his records, ensure results were followed up, co-ordinate between doctors and see that the right people were talking to each other. Pellizzer, his physician, was the one for the job and accompanied Walker to his first and subsequent infusions. At one stage he even joked that Pellizzer was director of "Walker Medical". "Some might think that's extravagance but when you're fighting for your life, it's cheap," says Walker.

Keytruda is given intravenously in two dosages, either 2mg/kg or 10mg/kg. Walker was given the higher dosage and would receive it every three weeks until mid-August 2014. Fortunately he had to make only one more trip to LA in February, after which a slot became available on an Australian trial at Westmead Hospital in Sydney. Keytruda acts quickly and patients who respond to the drug typically say they are feeling better after a few weeks. By Walker's fourth cycle, in April 2013, the tumours had begun to melt away. They had disappeared from his brain. The tumours on his lung and left adrenal gland had shrunk significantly. By January 2014 he was so encouraged by the results he addressed Merck's Australian staff at their conference at the Sydney Hilton. Seven months later he ceased infusions of Keytruda and in October, he was officially announced clear of cancer.

For McArthur the results are breathtaking and clear cut. "Without Keytruda Ron wouldn't be with us today," he says. Not everyone, however, is as lucky as Walker, says Hicks. "While we see a number of these very remarkable responses unfortunately it's a bit of a crapshoot of whether your immune system is able to be stimulated sufficiently to eradicate the tumours," he says. "In a sense Ron was very lucky; although he had lots of individual tumour deposits, each of them was relatively small."

Melanoma capital

Australia has the highest incidence of melanoma in the world. The Melanoma Institute Australia estimates 12,500 Australians were diagnosed with it last year, which is 12 times the global average. By 2020, the number of Australians diagnosed with melanoma is expected to grow to 17,750 cases annually as the population ages. However, there is hope that younger Australians, who benefited from the sun safety campaigns that started in the 1980s, may be the generation in which melanoma incidence begins to decline.

Australia's reputation as the world's melanoma capital is one reason why there's a strong push to fast-track cancer drugs, such as Keytruda, for market. Dr Susanne Fiedler, managing director of MSD Australia and New Zealand, and Frank Clyburn, president of Merck's (MSD) Global Oncology Business Unit, met with then-health minister Peter Dutton last year, as has McArthur. All made the case for Keytruda's use in Australia and the importance of its approval. "We're extremely confident there's a major benefit, which is why we want to see fast-tracking of the treatment," says McArthur. "Australian people want access to treatments like Keytruda and the onus is on our elected representatives to facilitate that happening and not to hide behind the bureaucratic process. We get concerned in the cancer community that a drug for high blood pressure is treated the same as Keytruda, which is going to save the lives of people with short life expectancy."

An Australian parliamentary inquiry into skin cancer received a submission from MSD in April that said based on current systems, Australian patients were expected to get access to Keytruda about 1.5 to two years after patients in the US. In November, MSD submitted its application for Keytruda to be put on the Pharmaceutical Benefits Scheme to treat patients with advanced melanoma. It will be considered by the Pharmaceutical Benefits Advisory Committee in March, but it needs to be registered by the Therapeutic Goods Administration before it can be listed on the PBS.

"From a government perspective there's a great openness to really do everything to get this product to patients," says Fiedler. Yervoy became available on the PBS in 2013. A spokeswoman for the Department of Health says the Abbott government is reviewing the process of approving drugs before they go on the PBS. It will receive the report from that review at the end of March. In late December, Sussan Ley replaced Dutton as Health Minister after a ministerial reshuffle.

Walker has become an outspoken advocate for reform of how the government approves cancer medicines. "We'll keep pushing and pushing until we get the proper result," he says. For governments, however, Keytruda is expensive. It costs $US12,500 ($15,360) per infusion and Walker's treatment alone tallied around $US350,000, which was absorbed by the trial. Pharmaceutical companies Roche and AstraZeneca are also in advanced stages of testing drugs that work similarly to Merck's Keytruda and Bristol-Myers Squibb's Opdivo. All those PD-1 drugs have been developed based on the ground-breaking research by four award-winning scientists based in Japan and the US. The competition among the pharmaceutical giants could force down the cost for these immunotherapy drugs, which governments would welcome.

Since Walker's cancer battle has become known he's been contacted frequently by people asking him how to get on the wonder drug. But he's quick to explain Keytruda is not a panacea. He doesn't want to give false hope. "A lot of people ring me up and say, 'Can you help, can you help me? I don't want to die'. I introduce them to the right doctor." Walker knows of at least two other prominent Australian businessmen who are on Keytruda for melanoma and lung cancer. "There's a lot of hope for a lot of people that have got cancer."

Pellizzer says one of the things that impressed her about Walker's cancer journey is how strongly he has been fighting to have Keytruda made available for others. "He got the drug and nobody would think any less of him if perhaps he just donated some money. The easiest thing in the world for him would have to been to write a cheque to Peter Mac [Peter Callum Cancer Centre] for $1 million or $10 million. Instead, he's taken it on board as a personal fight for people he doesn't even know and when he's unwell, he's giving of his time and energy. He didn't have to do that."

Walker's cancer story is one of determination, perseverance and how he almost didn't make it. He remains under the tight surveillance of his doctors. The results are incredible but it is early days. It remains to be seen whether Keytruda helps put patients into permanent remission or whether the cancer comes back. Cancer has returned in some patients treated with Keytruda. What the drug does offer patients such as Walker is hope that scientists are advancing on a cure for different forms of cancer. Cancer is hundreds of diseases and there will never be one silver bullet. But if there are one or two bullets for some cancers, it's a start.

As for Walker, he couldn't be happier. "It's absolutely an amazing situation that I'm so grateful for. Never before did I think it would be as successful as what's happened." He's celebrated two Christmases with his extended family at Sorrento, south of Melbourne, after being told he wouldn't make the first. In February, he will celebrate his 48th wedding anniversary. "If Ron is free of any growth of his melanoma in 10 years then we would say he's cured," says McArthur. Perhaps that's the next challenge Walker can set himself.

This story first appeared in The Australian Financial Review Magazine.