More than half of people diagnosed with advanced melanoma now survive for at least 10 years when they receive a double hit of immunotherapy drugs, a trial has found. The combined treatment has transformed survival rates for a form of skin cancer that once had a grim prognosis, with some patients now living long enough that they die from other causes. Fifteen years ago, only one in 20 patients with advanced melanoma survived for five years, with many dying within six to nine months of the condition being confirmed. “The definition of cure is to return someone to their normal life expectancy for their age and state of health,” said James Larkin, a consultant medical oncologist at the Royal Marsden NHS foundation trust and a professor at the Institute of Cancer Research. “Having treated a lot of these patients over the past 10 years it seems that some are cured: they’re back to their normal lives, they’re getting on with things.” More than 20,000 people are expected to be diagnosed with melanoma in the UK this year, a record high that is largely being driven by rising cases in older people. The vast majority of cases are preventable and caused by too much exposure to UV light. The trial explored two drugs, ipilimumab and nivolumab, both immune checkpoint inhibitors, in 945 patients with stage 3 or 4 melanoma, where tumours were spreading. The drugs work by disabling “brakes” built into the immune system to prevent it from turning on healthy tissues. Cut the brakes and the immune system can recognise and attack the cancer cells. The approach is highly effective. Results presented at the European Society for Medical Oncology in Barcelona on Sunday, and published in the New England Journal of Medicine, show that the melanoma-specific survival rate for patients in the trial was higher than the overall survival rate, meaning they were starting to live long enough to die from other causes. At 10 years, the melanoma-specific survival rate for patients treated with both drugs was 52%. Larkin called the results “remarkable”. Many toxic anti-cancer drugs that destroy tumours cells stop working over time, but the response to immune checkpoint inhibitors is long-lasting. The trial marks the longest follow-up to date of patients receiving the drugs for advanced melanoma, giving doctors crucial information on how long the treatment is effective for, the overall survival rates and side-effects. While some patients experienced side-effects early on, no new problems arose later. Patients who stopped treatment early because of significant side-effects still benefited from the combination therapy, as the drugs had already taken effect on their immune systems. Lucy Davis, 47, joined the trial funded by Bristol-Myers Squibb, the drug manufacturer, after being diagnosed in 2011 with stage 3 melanoma. She had surgery to remove the cancer and surrounding lymph nodes, but two years later was told the disease had progressed to stage 4 and she had only months to live. “Before I started the trial I was really ill, I could barely eat, I was losing weight and was in a lot of pain, but three months later I felt completely different, my appetite was back and scans showed that the treatment was working,” Davis said. “My children were five and seven years old when I received the news that I had just months to live; and they are now 16 and 18. I have been able to see them complete their exams and go to college, which is absolutely amazing.” While the results are impressive, efforts are now focused on the substantial portion of patients who do not respond to the immunotherapies. It is unclear why the drugs fail in many patients, and there is probably no single answer, with roles for the biology of the patient’s tumour and their immune system. Larkin said: “It’s great to see these data from a disease where 15 years ago average life expectancy was six to nine months. But we still have a significant group of people in the clinic who do not respond to this treatment. Where we’re focusing our energies as a field, in melanoma and in other cancers, is to try and understand that: why aren’t these people responding?” Dr Sam Godfrey, the science engagement lead at Cancer Research UK, said: “Over the last decade, there have been big improvements in survival for people with advanced melanoma skin cancer, partially because of the introduction of a group of immunotherapy drugs called checkpoint inhibitors. “This study indicates that combining two of these checkpoint inhibitors led to more people surviving their disease for 10 years or more. Promising results like this show how vital ongoing research into cancer is, to help people live longer, better lives.”