A new, potent drug combination may cure some melanomas
A new study suggests that one in five melanoma patients treated with a pair of immunotherapy drugs, ipilimumab and nivolumab, might be cured of their disease.
Furthermore, 69% of the 142 study patients were still alive after two years. Melanoma is the most dangerous type of skin cancer and the sixth most common cancer in the UK, killing more than 2,000 people each year.
Immunotherapy refers to treatment that encourages the patient’s immune system to attack cancer cells. Original, but relatively unsuccessful forms of this treatment involved the use of anti-tumour “vaccines” based on proteins produced specifically by cancer cells, or even whole cells that had been inactivated. More recently a radically different and far more effective approach has been taken, which involves removing the naturally occurring inhibitors or “breaks” acting on the immune system. One of the most important of these is the PD-1 ligand that binds to the PD-1 protein on the surface of T-cells, which are immune cells that can invade tumours and selectively kill cancer cells.
Tumours that make PD-1 ligand are able to switch T cells to an inactive state, blocking the immune response. Nivolumab is an antibody that binds to PD-1 and prevents this interaction between cancer cells and T-cells, hence promoting the destruction of the tumour. Ipilimumab also helps take the break of the immune system but has a different mechanism of action; instead of disrupting the interaction between T-cells and cancer cells it blocks an inhibitory circuit that exists between two different immune cells – dendritic cells and T cells – through binding to a protein called CTLA4.
The logic of combining these drugs in a clinical trial was to enhance the killing of cancer cells, thereby destroying more of the tumour than either drug could on its own.
The results of the new trial published in the Journal of the American Medical Association suggests that this approach can be successful. However, both ipilimumab and nivolumab are associated with significant side effects, and this was also reflected in the new trial, as around 50% of the patients had to stop treatment due to life-threatening side effects. Side effects are often more difficult to manage with drugs that act on the immune system as the changes that occur sometimes take a long time to reverse after treatment has finished, and indeed, in some cases, the immune system may never fully return to its original state. These problems can be made still worse by the nature of the drugs themselves; antibodies can persist for many months in the body, unlike other types of drugs that are usually gone in a few days.
Further refinements of this very promising approach are therefore needed before it can form the basis of a safe and effective treatment.