Tests showed new generation of drug that frees immune system to attack devastating form of lung cancer doubled life expectancy of certain patients.
A drug that frees the immune system to attack a devastating form of lung cancer has been shown to double the life expectancy of a targeted group of patients.
Nivolumab is one of new generation of immunotherapy drugs that release cancer-applied brakes on the immune system called “checkpoints”. The results, from an 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 licensed 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).
The disease accounts for about 85% of all cases of lung cancer, which is diagnosed in 43,463 new patients and causes 35,371 deaths each year in the UK. Overall, nivolumab reduced the risk of dying by 27% compared with docetaxel and increased typical survival time from 9.4 to 12.2 months.
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% of patients had measurable levels of the protein.
The trial, conducted in North America and Europe, was halted early on ethical grounds because of the strong results. It was led by Dr Luis Paz-Ares from the Hospital Universitario Virgen Del Rocio, in Seville, Spain.
Commenting on the findings presented at the annual meeting of the American Society of Clinical Oncology in Chicago, Dr 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.
This is the first time we have seen Phase III immunotherapy data report survival benefit in this difficult to treat disease.
For patients that have limited treatment options, it is very encouraging to see the early benefits immunotherapies such as nivolumab can have, and is just the beginning of the journey to further improve and refine these new treatments.”
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.
Dr Alan Worsley, senior science information officer at Cancer Research UK, said: “Harnessing the power of our immune system to fight cancer will be an essential part of future treatments.
This trial shows that blocking lung cancer’s ability to hide from immune cells may be better than current chemotherapy treatments. Advances like these are giving real hope for lung cancer patients, who have until now had very few options.”
The CheckMate 057 trial also showed that nivolumab caused fewer serious side-effects than docetaxel. Severe side-effects were reported in 10% of patients in the nivolumab group compared with more than half of those treated with the chemotherapy agent.
Because of the way they work, checkpoint inhibitors can trigger adverse effects linked to autoimmune reactions.
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 licensed in the US to treat a different form of lung cancer, squamous non-small cell lung cancer, under the brand name Opdivo. It was approved by US regulator the Food and Drug Administration in a record five days after the licence application was submitted by the pharmaceutical company Bristol-Myers Squibb. Licences allowing the drug to be used to treat lung cancer and melanoma skin cancer in Europe are expected soon.[hr]