The molecular make-up of lung tumours could help identify patients who might benefit from immunotherapy treatment up front, a new study has found.
The phase 3 clinical trial, run by The Ohio State University Comprehensive Cancer Center in the US, suggests that immunotherapy given before other drugs could improve the outlook for certain patients with advanced lung cancer.
The findings are “an important step forward” in understanding which patients are likely to benefit from immunotherapy, said lead scientist Dr David Carbone.
The immunotherapy drug used in the trial – called nivolumab (Opdivo) – is already available on the NHS for some patients with advanced lung cancer who have previously been treated with chemotherapy.
The latest trial compared nivolumab with standard chemotherapy in 530 patients who hadn’t been treated with cancer drugs previously.
Nivolumab works by blocking an immune molecule called PD-1, which normally prevents the immune system from going into overdrive, but in some cancers is overproduced. Targeting this molecule releases the immune system’s ‘brakes’ so that it can attack the tumour.
The patients all had advanced lung cancer or lung cancer that had returned, and their tumour cells carried PD-1’s molecular partner PD-L1 on their surface, indicating that PD-1 blockers could be effective for them.
Overall, survival and the length of time until the disease worsened were similar between patients receiving either immunotherapy or chemotherapy. But when the researchers took into account certain characteristics of the tumours, immunotherapy showed benefits over chemotherapy.
In patients whose tumours had high levels of the PD-L1 molecule and lots of immune-stimulating genetic faults, 3 in 4 patients’ tumours (75%) responded to nivolumab, compared with just 16% in those who had low levels of both. Only around 1 in 4 patients in these groups responded to chemotherapy. In addition, patients treated with nivolumab experienced fewer side effects than those given chemotherapy.
The results have been published in The New England Journal of Medicine.
Professor Charles Swanton, a Cancer Research UK expert on lung cancer, said: “Finding ways to predict whether immunotherapy will benefit patients is critical to improve survival. This study emphasises the need to characterise patients’ tumours to guide the design of clinical trials for cancer immunotherapies.”
To make sure that these important drugs reach patients who are most likely to benefit from them, Swanton says, future studies need to look into the role of the number of genetic faults within a tumour and select patients whose PD-L1 levels are above a certain level.
“This will have the added benefit of limiting costs and side effects of treating patients who won’t benefit from this class of immune therapy,” he added.
Carbone, D. P. et al. (2017). First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. The New England Journal of Medicine. DOI: 10.1056/NEJMoa1613493.