A newly developed ‘electronic nose’ can measure chemicals in the breath of small cancer lung patients to determine if they will respond to immunotherapy treatment.

Immunotherapy is Changing Cancer Care
Immunotherapy treatments harness the body’s immune system to fight the cancer cells, which is transforming the treatment of advanced stage cancers. However, only a small subset of patients respond well to immunotherapy. The immunotherapy drug nivolumab, for example, targets the PD-1 receptor on the body’s T-cells. Tumour cells can express the ligand to PD-1, which can bind to PD-1 on the immune cells. If PD-1 binds to its ligand on a cancer cell, it recognises it as a body cell, not foreign, and does not make it undergo programmed cell death. Nivolumab binds to PD-1 so the tumour cells are not able to disguise themselves from the immune system, allowing the cancer destroyed.

Therefore, if the patient’s cancer cells are expressing the PD-1 ligand then nivolumab treatment will likely be very effective. However, if the patient’s cancer cells are not expressing the PD-1 ligand, nivolumab will not be an effective treatment for them.

Choosing Immunotherapy Patients
There is currently non-invasive method to distinguish patients who will respond to nivolumab immunotherapy from those who will not. The eNOSE can detect volatile organic compounds (VOC) that make up 1% of patient’s breath. As the proportion of different VOCs exhaled can depend on the metabolic processes taking place in the lung, the researchers investigated if a patients VOC profile could predict if they would respond to immunotherapy treatment.

143 patients with advanced non-small cell lung cancer participated in the trial. Each participant underwent the eNOSE breathalyser test before undergoing an immunotherapy treatment with either nivolumab or pembrolizumab. After three months, their tumour size was evaluated to determine if they had responded to the immunotherapy treatment. Dr Mirte Miller, one of the first authors from the study, said ‘We found that before the start of treatment with immunotherapy, the eNose analysis of exhaled breath from the patients with non-small cell lung cancer could distinguish between responders and non-responders with an accuracy of 85%.’

Getting the Right Treatment
There is therefore strong evidence that the eNOSE can be used to distinguish non-small lung cell cancer patients who should undergo immunotherapy from those who should undergo alternative treatments. Although immunotherapy generally has less side-effects, a small proportion of patients can experience particularly severe side-effects. The eNOSE can enable patients for whom immunotherapy will not be effective to avoid these side-effects.
The study is therefore a major step forward for precision medicine, enabling patients to be assigned to the treatments that will benefit them the most.