Half of patients with advanced melanoma survive for 10 years with dual drug therapy
A study has found that more than half of people diagnosed with advanced melanoma live for at least 10 years if they receive a double dose of immunotherapy drugs.
The combined treatment has led to a dramatic improvement in survival rates for a form of skin cancer that previously had a bleak prognosis, with some patients now living so long that they die of other causes.
Fifteen years ago, only one in 20 patients with advanced melanoma survived five years. Many died within six to nine months of being diagnosed.
“The definition of a cure is to return someone to their normal life expectancy for their age and 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 many of these patients over the last 10 years, it does seem that some are cured: they are back to their normal life, they are getting on with their life.”
More than 20,000 people in the UK are expected to be diagnosed with melanoma this year, a record high largely driven by an increase in cases in older people. The vast majority of cases are preventable and are caused by too much exposure to UV light.
The trial tested 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 turning off “brakes” that are built into the immune system to prevent it from attacking healthy tissues. When you cut the brakes, 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 began living long enough to die from other causes. After 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 tumor cells stop working over time, but the response to immune checkpoint inhibitors is long-lasting.
The trial marks the longest follow-up yet of patients receiving the drugs for advanced melanoma, and will give doctors crucial information about how long the treatment is effective, overall survival rates and side effects. Although some patients experienced side effects early on, no new problems developed later. Patients who stopped treatment early because of significant side effects still benefited from the combination therapy because the drugs had already taken effect on their immune systems.
Lucy Davis, 47, joined the trial funded by Bristol-Myers Squibb, the drug’s maker, after being diagnosed with stage 3 melanoma in 2011. She underwent surgery to remove the cancer and surrounding lymph nodes, but two years later she was told the disease had progressed to stage 4 and she had just months to live.
“Before I started the trial I was really sick, 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 the treatment was working,” Davis said. “My children were five and seven when I got the news that I only had a few months to live; they are now 16 and 18. I’ve seen them finish their exams and go to university, which is absolutely amazing.”
While the results are impressive, efforts are now focused on the substantial proportion of patients who do not respond to immunotherapies. It is unclear why the drugs fail in many patients, and there is likely no single answer, with the biology of the patient’s tumor and their immune system playing a role.
Larkin said: “It’s great to see these data in 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 don’t respond to this treatment. Where we focus our energies as a field, in melanoma and other cancers, is to try to understand why these people don’t respond?”
Dr Sam Godfrey, head of scientific engagement at Cancer Research UK, said: “Over the past decade, survival rates for people with advanced melanoma skin cancer have improved dramatically, partly thanks to the introduction of a group of immunotherapy drugs called checkpoint inhibitors.
“This study suggests that combining two of these checkpoint inhibitors helped more people survive their disease for 10 years or more. Promising results like these show how important ongoing cancer research is to help people live longer and better.”