Half of patients with advanced melanoma survive 10 years with dual drug treatment | Skin cancer

According to a study, more than half of patients with advanced melanoma now survive for at least ten years if they receive a double dose of immunotherapy drugs.

Combined treatment has improved survival rates for a form of skin cancer that previously had a dismal prognosis; some patients now live long enough to die from other causes.

Fifteen years ago, only one in 20 patients with advanced melanoma survived the first five years; many died within six to nine months of being diagnosed with the disease.

“The definition of a cure is to give someone back their normal life expectancy for their age and health,” said James Larkin, consultant medical oncologist at the Royal Marsden NHS Foundation Trust and professor at the Institute of Cancer Research. “Having treated many of these patients over the last decade, it seems that some are cured: they have resumed their normal lives and are coping with things.”

More than 20,000 people are expected to be diagnosed with melanoma in the UK this year, a record high largely due to the increasing number of cases in older people. The vast majority of cases are preventable and caused by too much UV light.

The study tested two drugs, ipilimumab and nivolumab, both immune checkpoint inhibitors, in 945 patients with stage 3 or 4 melanomas whose tumors had spread. The drugs work by disabling the “brakes” built into the immune system to prevent it from targeting healthy tissue. When the brakes are released, the immune system can recognize and attack the cancer cells.

The approach is very effective. Results presented on Sunday at the European Society for Medical Oncology in Barcelona and published in the New England Journal of Medicine show that the melanoma-specific survival rate of patients in the study was higher than the overall survival rate. That is, they slowly lived long enough to die of other causes. After 10 years, the melanoma-specific survival rate of patients treated with both drugs was 52%.

Larkin called the results “remarkable.” Many toxic cancer drugs that destroy tumor cells lose their effectiveness over time, but the effects of immune checkpoint inhibitors are long-lasting.

The study is the longest follow-up to date of patients receiving the drugs for advanced melanoma. It provides doctors with important information about the duration of treatment's effects, overall survival rates and side effects. While some patients experienced side effects at the beginning, no new problems arose later. Patients who stopped treatment early because of significant side effects still benefited from the combination therapy because the drugs had already acted on their immune systems.

Lucy Davis, 47, took part in the study funded by drugmaker Bristol-Myers Squibb 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 was already stage 4 and she had just months to live.

“Before I started the trial I was really sick, I could hardly eat, I was losing weight and 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; and now they are 16 and 18. I have been able to watch them finish their exams and go to college, which is absolutely amazing.”

Although the results are impressive, efforts are now focused on the significant proportion of patients who fail immunotherapies. It is unclear why the drugs fail in many patients, and there is probably no single answer. The biology of the tumor and the patient's immune system play a role.

Larkin said: “It's great to see these data on 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 are not responding to this treatment. What we as a field are focusing our energies on, in melanoma and other cancers, is trying to understand: Why are these people not responding?”

Dr Sam Godfrey, head of science at Cancer Research UK, said: “Over the last decade, survival rates for people with advanced melanoma have improved significantly, partly due to the introduction of a group of immunotherapy drugs called checkpoint inhibitors.”

“This study shows that combining two of these checkpoint inhibitors has resulted in more people surviving their disease for ten years or more. Promising results like this show how important ongoing cancer research is to help people live longer and better.”