A new development in cancer treatment has been reported as showing impressive results for terminally ill patients with melanoma
For decades immunotherapy - getting the body’s own immune system to destroy cancerous cells in the body - has been little more than an aspiration. It has been a longstanding mystery in the scientific community why the body’s own defensive immune system is not able to attack cancer cells in the same way that it would fight a cold virus. After decades of research, scientists have discovered that cancer, just like the human immunodeficiency virus (HIV), is able to evade the T-cells that find and kill harmful cells, due to molecules from both types of cell interacting to persuade the T-cells not to attack.
In 1992, Japanese scientists identified a molecule on the T-cells that was partly responsible for their failure to attack cancer cells, which they named ‘programmed death 1’, or PD1. This discovery prompted further research into the behaviour of T-cells, why they were unable to destroy cancer cells and into how to tackle this problem. The new drugs are the eventual result of this research. At this early stage of the trial they seem to be working. Unlike similar drugs, their use is not likely to be restricted to treating melanoma, opening up possibilities for the treatment of numerous different types of cancer.
The international trial was led by the Royal Marsden Hospital in London. It involved 945 patients with advanced melanoma who were considered terminally ill with very short life expectancies. Ipilimumab and nivolumab was used to treat these patients and was found to shrink tumours in 58%. There is hope that these tumours might disappear altogether. Around a fifth of the patients responded to the drug ipilimumab when it was given in isolation from nivolumab. Results from the trial were published in the New England Journal of Medicine and announced in Chicago, at the American Society for Clinical Oncology (ASCO) annual meeting in 2015.
There are currently two reasons to be cautious about the long-term viability of this treatment. First, the side-effects of utilising the body’s own immune system to fight off the cells have proved severe. Nell Barrie, of Cancer Research UK (CRUK), said “your immune system is designed normally not to attack your body’s own cells. You have to boost the immune system beyond its normal function and you are going to sensitise the immune system. It’s very, very complex.” Some patients were unable to cope with the severity of the side effects, which include feeling extremely sick, and were unable to continue with the trial. Dr Alan Worsley, also from CRUK, has said that the key to making this treatment successful is to identify which patients are most likely to benefit from combination immunotherapy.
Secondly, there is the question of whether these treatments can actually cure cancer or whether it is a question of determining the length of time during which the treatments prevent the cancer from progressing. There is an unfortunate precedent for taking a pessimistic view of this issue. There have been melanoma drugs in the past that were treated as ground-breaking cures. These ‘targeted drugs’, the BRAF inhibitors, caused tumours to disappear completely. However, after a few months, the cancer returned more aggressively than before and the patients died.
It is too soon for scientists to know whether or not these treatments will have a big impact on survival rates. But the ultimate aim is for immunotherapy to be used to teach the body’s immune system to recognise and destroy cancer cells, preventing the chance of recurrence of the cancer.
Ipilimumab was approved by NICE (the National Institute for Health and Care Excellence) for advanced skin cancer patients in December 2012, despite the cost, as the company selling it agreed to give the Department of Health a reasonable discount. Nivolumab is likely to get its licence in the summer of 2015, but whether an acceptable price for it can be successfully negotiated with the company remains to be seen.
“This research is so exciting as it suggests immunotherapy treatments could be combined to support our immune systems in their fight against advanced melanoma.”