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 to die of 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 being diagnosed with the condition.
“The definition of cure is to return someone to their normal life expectancy for their age and health condition,” said James Larkin, a consultant medical oncologist at the Royal Marsden NHS Foundation Trust and a professor at the Institute of Cancer Research. “After many of these patients have been treated over the last 10 years, some seem to be 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 largely driven by rising cases in older people. The vast majority of cases are preventable and are caused by too much exposure to UV light.
The trial examined two drugs, ipilimumab and nivolumab, both immune checkpoint inhibitors, in 945 patients with stage 3 or 4 melanoma, where tumors had spread. 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 recognize 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 Medicineshow that the melanoma-specific survival rate for patients in the trial was higher than the overall survival rate, meaning they started living long enough to die of 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 anticancer drugs that destroy tumors stop working over time, but the response to immune checkpoint inhibitors is long-lasting.
The trial is the longest follow-up to date of patients who received the drugs for advanced melanoma, giving doctors important information about how long the treatment is effective, overall survival rates and side effects. While some patients experienced side effects early on, no new problems arose later. Patients who discontinued treatment early due to 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 maker, after being diagnosed with stage 3 melanoma in 2011. 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 only had months to live.
“Before I started the trial I was really sick, I could barely eat, I lost 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 only had months to live; and they are now 16 and 18. I could see them finish their exams and go to university, which is absolutely amazing.”
Although the results are impressive, efforts are now focused on the significant 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 tumor and their immune system.
Larkin said: “It’s great to see this data from a disease where 15 years ago the 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 energy as a field, in melanoma and in other cancers, is trying to understand: Why are these people not responding?”
Dr Sam Godfrey, the leader of science engagement at Cancer Research UK, said: “Over the last decade there have been huge improvements in survival for people with advanced melanoma skin cancer, partly due to the introduction of a group of immunotherapy drugs called checkpoint inhibitors become.
“This study indicates that the combination of two of these checkpoint inhibitors resulted in more people surviving their disease for 10 years or more. Promising results like these show how vital ongoing cancer research is to helping people live longer, better lives.”
