‘The sky’s the limit’: how Australian scientists rewrote the cancer script
A big shift in treatment is set to dramatically increase the survival rates of patients with melanoma, paving the way for a revolution in how other cancers are dealt with.
The treatment of advanced melanoma will be radically overhauled in Australia, with immune therapies to be given before surgery instead of after – a shift set to improve survival rates greatly.
The pre-surgery use of combination immunotherapy for high-risk melanoma, a strategy that will now be publicly funded for all Stage 3 patients, is being described as “a revolution in cancer therapy” and is set be replicated across the globe as well as transforming the treatment of a suite of other cancers.
World-first clinical trials led by Melanoma Institute Australia in conjunction with academic colleagues in the Netherlands found giving combination checkpoint inhibitors prior to surgery, known as neoadjuvant therapy, was far more effective than the current standard post-surgery approach, which uses a single-agent drug.
The new therapy gave the body the best opportunity to activate its own cancer-fighting defences.
The approach, pioneered by MIA medical director Georgina Long AO, was proved effective in the global NADINA clinical trial, which showed estimated 12-month event-free survival rates of almost 84 per cent in patients with Stage 3 melanoma who were treated with combination immunotherapy prior to surgery. That compared with a 57 per cent survival rate achieved by the current standard of care.
“This is a cancer-treatment revolution,” Professor Long said. “This is huge, and it speaks to the idea of leveraging the immune system in the most optimal way for cancer. It’s a major step forward in a history of incremental steps aiming to cure cancer.”
Immunotherapy prior to surgery may have applications for some of the most deadly cancers, including glioblastoma, pancreatic cancer and triple-negative breast cancer, lung cancer, renal cell carcinoma, some head and neck cancers and some colon cancers.
“The sky’s the limit at this point, because this is just the first trial,” Professor Long said.
“This is a wonderful paradigm to push cancer research and cure forward.”
The Pharmaceutical Benefits Advisory Committee released a determination late on Friday that it had approved pre-surgical use of the combination immunotherapy drugs nivolumab and ipilimumab to be listed as a treatment to be funded for Stage 3 melanoma on the Pharmaceutical Benefits Scheme. The PBS listing, to follow in coming months, will open the way for the new method of treating high-risk melanoma patients to be available for all affected sufferers. It places Australia as the first country in the world to support neoadjuvant immune treatment for Stage 3 melanoma as the publicly funded standard of care.
Professor Long, joint Australian of the Year last year with now terminally ill pathologist Professor Richard Scolyer, said: “I am delighted by the PBAC’s decision … Australia is leading the way in revolutionising cancer treatment across the globe. NADINA shows the power of clinical trials to push science and medicine forward, and move us closer to our goal of reaching zero deaths from melanoma and saving lives across all cancers.”
The pioneering step came after 423 patients participated in the landmark NADINA trial, a third of them in Australia across eight hospitals in NSW, Victoria, Tasmania and Western Australia. The MIA sponsored the trial together with the Netherlands Cancer Institute. An investigator-led trial that leads to publicly funded therapies is rare.
One of the patients treated with combination immunotherapy prior to surgery was Sydney teacher Fiona Mahon, who was diagnosed with Stage 3 melanoma at the age of 39. Ms Mahon initially had surgery to remove a melanoma on her back as well as a lymph node, but the cancer returned. When she joined NADINA in 2023, Ms Mahon was given combination checkpoint inhibitor drugs, and then underwent scans a couple of months later prior to her second round of surgery.
“I had scans before my surgery, and they couldn’t find any traces of melanoma left in my lymph nodes,” Ms Mahon said. “Then they removed my lymph nodes in my neck, and there was no trace of cancer in any of them in the testing process, so I didn’t actually have to have any more treatment. They told me that the chance of a recurrence after that was minimal, like single figures. It was just complete relief.
“You only have to Google melanoma to see that even 10 years ago, I probably wouldn’t have survived.”
Australia has the highest melanoma rates in the world with one person diagnosed with the disease every 30 minutes and one dying from it every six hours. Prior to incredible advances in immunotherapy, melanoma was often a death sentence.
The reason giving immunotherapy prior to surgery rather than after is so effective is because the body’s immune system responds much more powerfully when it can “see” the enemy. Checkpoint inhibitors do not kill cancer cells directly but rather prime the body’s immune system to kill errant cells by triggering a supercharged T-Cell response that is specific to the particular tumour or tumours.
Immunotherapy given prior to tumours being surgically removed triggers stronger and more diverse T-Cell responses, given these immune cells are responding to the entire tumour and what is known as its complete neoantigen repertoire, made up of unique protein fragments on cancer cells that the immune system can recognise.
“If the immune system can see what it’s targeting, it’s easier to target the cancer cells,” Professor Long said. “And the other aspect of this is we get a much better immune system memory response.”
The stunning event-free survival rates from Phase 3 of the NADINA trial were presented at the American Society of Clinical Oncology and published in the New England Journal of Medicine last year. Since then, an 18-month update reporting participants’ distant metastasis-free survival – or how long patients remained free of secondary tumours – was presented at the European Society of Medical Oncology. That showed 85.7 per cent of those given neoadjuvant therapy had remained cancer-free 18 months after treatment.
Ms Mahon, who is now 43, says she has the work of Australia’s leading scientists to thank for her life. She is thrilled that other patients will now be able to affordably access similar treatment.
“I think it’s amazing,” she said. “The cost of the treatment if you have to fund it yourself is astronomical, and we obviously have the highest rates of skin cancer in the world in Australia. So the fact that there’s a drug like this that can literally save people’s lives, I think it’s amazing that everyone has access to it now.”
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