The mystery of resistance - Nathan's story
Family man Nathan Giles tragically lost his battle with melanoma in June last year. He was just 38 years old. Nathan was given access to treatments that extended his life by five years – giving him precious time with his family including five young children.
But why did Nathan develop resistance to treatment that was initially helping him?
It all began in 2006 when Nathan’s mum found a dark mole on his neck, which was removed, and at the time, was not too much of a concern. Five years later, he started to experience increasing lethargy and stomach pain. Nathan’s life changed forever in September 2011 when a CT scan confirmed he had Stage IV melanoma in his liver, lungs and brain. Nathan was given less than six months to live.
The team at Melanoma Institute Australia worked to give Nathan as much time as possible with his wife Jenny and their young family of five children. Nathan wanted to be around for his youngest son, Hamish, who was only two months old, to be able to remember him.
“During his five-year battle, Nathan had to give up teaching,” said his father Roger. “He lost his independence because he couldn't drive and he lost his mobility which meant he couldn't play with his children. But he remained steadfast as a husband and father. He was always thankful for every extra day he had with his wife and young children.”
Just one week after his diagnosis, Nathan’s brain lesion caused him to lose movement in his right hand. He underwent brain surgery and started his first targeted therapy, dabrafenib (Tafinlar®) to stop the melanoma tumours from growing. For a few months, Nathan made good progress.
“With patients on targeted therapies, the day after they begin treatment, they often have incredible clinical benefit or a change in response that can be seen right away,” said Melanoma Institute Australia’s Conjoint Medical Director, Professor Richard Scolyer.
But Nathan’s brain tumours soon grew again, as they had become resistant to the targeted therapy. Brain radiotherapy halted the growth of his brain lesions, but the tumours in Nathan’s body started to grow so his oncologist switched him to the immunotherapy, ipilimumab (Yervoy®).
Nathan remained on this immunotherapy for a few months until he collapsed at home in June 2012 when one of his brain lesions bled. Over the next 18 months, he had more brain radiotherapy and surgery and after experiencing a major seizure Nathan was started on a combination of dabrafenib and trametinib (Mekinist®) to help shrink the brain metastases.
Unfortunately, Nathan continued to deteriorate. But hope arrived in July 2014, when Nathan was one of the first Australians to receive compassionate access to the new immunotherapy, pembrolizumab (Keytruda®), which again, worked for him initially.
“The response was dramatic. Within three weeks Nathan's brain lesions began to shrink for the first time! I can still remember the smile on his neurosurgeon’s face. He had never seen such a positive response,” said Roger.
Nathan resumed treatment with dabrafenib and trametinib and a year went by without incident.
“At long last Nathan's quality of life started to improve,” remembers Roger. “We began to have hope that we could turn this terrible illness into a chronic disease.”
Nathan was at home in December 2015 when he had a major seizure caused by brain swelling. His medication was adjusted again and his melanoma seemed to remain under control until May 2016 when sadly his brain lesions bled once more.
Nathan lost his battle on 8 June 2016 at just 38 years of age.
Nathan was given access to treatments that extended his life by five years. These treatments can be very effective in treating some melanoma patients, but like Nathan, 70% of patients who initially respond develop resistance over time.
Melanoma Institute Australia is committed to further research to understand why acquired resistance occurs, and importantly, to help overcome it.