A drug that frees the immune system to attack a devastating form of lung cancer has been shown to double the life expectancy of genetically targeted patients.
Nivolumab is one of new generation of immunotherapy drugs that release cancer-applied brakes on the immune system called ‘checkpoints’.
The results, from a major international trial involving patients who had already been treated for the most common form of lung cancer, were described by one expert as a “paradigm shift”.
In the Phase III trial, the last step before a drug is licenced for use in clinics, researchers compared the effectiveness of nivolumab and the standard chemotherapy drug docetaxel in 582 patients with advanced non-squamous non-small cell lung cancer (NSCLC).
As in the rest of Europe, lung cancer is the most prevalent form of cancer in Malta, affecting more men than women. Recent figures show the disease killed 45 Maltese men per 100,000 against just 10 per 100,000 females.
Overall, nivolumab reduced the risk of dying by 27 per cent compared with docetaxel and increased typical survival time from 9.4 to 12.2 months.
But the drug was found to be most effective in patients whose cancers produced higher levels of a tumour protein called PD-L1, potentially paving the way to personalised treatments.
For those with the most active PD-L1 gene in their cancer cells survival time more than doubled from eight to 19.4 months.
Lower “expression levels” led to life extensions of 10 months and eight months as amounts of the molecule reduced, while patients with little or no PD-L1 saw no survival benefit. Almost 80 per cent of patients had measurable levels of the protein.
Commenting on the findings presented at the annual meeting of the American Society of Clinical Oncology in Chicago, David Chao, consultant medical oncologist at the Royal Free Hospital, London, said: “This announcement marks a paradigm shift in the treatment of lung cancer, the biggest cancer killer in the UK.
Nivolumab is a ‘checkpoint inhibitor’ designed to overcome the ability many cancers have of shielding themselves from the immune system.
One way they do this is by switching on a safety mechanism whose normal function is to stop the immune system launching ‘friendly fire’ attacks on the body’s own cells.
PD-L1 is the molecular ‘finger’ or ‘ligand’ cancers use to press the checkpoint switch, which prevents the deployment of immune system T-cells that would otherwise target them.
Nivolumab – a type of synthetic antibody – blocks this pathway and stands in the way of the ‘finger’ to prevent the switch being pressed. It does this by binding to the switch, a receptor protein on surfaces of immune system cells called PD-1.
Jesme Fox, medical director at Roy Castle Lung Cancer Foundation, said: “There is much optimism that immunotherapy will provide a new treatment paradigm for patients with advanced non-small cell lung cancer. We welcome new research and the development of new therapies in this area.
“Lung cancer remains a devastating disease, with the vast majority of patients diagnosed when the disease is in the late, non-curative stage. It is for this reason that new and innovative therapies are of great need.”
Nivolumab is already licenced in the US to treat a different form of lung cancer.
Licences allowing the drug to be used to treat lung cancer and melanoma skin cancer in Europe are expected soon.