Hayley’s melanoma came back. Then scientists tried something different

Hayley Hetherington rarely thought about melanoma after she had one removed from the back of her scalp in 2019.

Life got busy. She started a new job, her father was sick back home in the UK and COVID was making everything from travel to medical checkups a small nightmare.

Professor Georgina Long, co-medical director of the Melanoma Institute Australia, and Hayley Hetherington, a teacher from Fairlight who participated in the worldwide trial.Credit: Edwina Pickles

In July 2022, during a six-monthly skin check, she asked her doctor about a lump on the back of her head. A biopsy confirmed the cancer had reappeared and spread to her lymph nodes. She was diagnosed with stage three melanoma.

“It was very scary, and worrying,” she said. “It just takes one or two little melanoma cells to escape the original thing and that’s it.”

Hetherington was referred to Professor Georgina Long, the Melanoma Institute Australia’s co-medical director, who put her on a phase three clinical trial testing the efficacy of immune therapy given before, rather than after, surgery.

Results from the trial, published on Sunday in the New England Journal of Medicine, showed a significant decrease in the rate of cancer progression before surgery, recurrence after surgery and death in stage three melanoma patients who had neoadjuvant (pre-surgery) immunotherapy, when compared with patients who received the conventional treatment post-surgery.

The groundbreaking study sets the stage for pre-surgery immunotherapy to become the global standard approach to combating melanoma, and lays the groundwork for new treatments to fight other cancers, said Professor Christian Blank, a pioneering immunotherapy researcher at the Netherlands Cancer Institute who co-led the international trial alongside Long.

“By using combination checkpoint inhibitor immunotherapy before rather than after surgery, we now have the clinical proof needed to change treatment protocols,” said Blank, who will present the findings at the American Society of Clinical Oncology conference in Chicago this week.

One-third of the 423 patients were Australian. Of the 212 patients randomised into the neoadjuvant arm of the trial, 83.7 per cent made it to 12 months “event-free”, compared to 57.2 per cent in the control cohort (in clinical trials, an “event” occurs if the cancer progresses before surgery, reoccurs after surgery, or if the participant dies).

Hetherington, one of the 212, received two infusions of combination immunotherapy three weeks apart and the treatment “packed a punch” – Hetherington spent a week in hospital with a bad fever, a known side effect of the treatment. However, her immune response was almost immediate; when it came time for surgery, the lump had shrunk so much she could barely feel it.

Her surgeon told her she had a complete metabolic response, meaning there were no cancer cells left in her body.

In the words of Long, her immune system had “gobbled it up”.

“Just like when you have a virus, the virus goes away because your body destroys it,” said Long, citing evidence from earlier clinical trials that had strongly suggested the body builds stronger and more targeted cancer-fighting cells if the full tumour is present when the immunotherapy is given.

Long was named the 2024 Australian of the Year alongside friend and colleague, Professor Richard Scolyer, for their work turning a diagnosis of advanced melanoma from a death sentence into a curable disease for more than half of patients.

The results presented a positive step in curing the other 50 per cent of patients, but Long said the next challenge will be identifying biomarkers that would help tailor drugs and dosage amounts to the individual and their cancer.

“We would hope that we can get to a point where a lot of patients don’t even need surgery,” she said. “There’s just so many gains – better quality of life for patients, less anxiety, fewer dollars spent … it’s just brilliant.”

Hetherington takes pride in contributing to a trial that will give patients around the globe a better chance of beating cancer.

“I’m hopeful that it will help people, and I’m super grateful that I’m living in a country where I’ve got access to the best medical care and the top experts in the world in melanoma,” she said. “It sounds like a strange thing to say, but I can’t believe my luck.”

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