METIS was a pivotal phase III trial that sought to determine if tumour treating fields therapy could meet the therapeutic need of delaying intracranial progression without negatively impacting neurocognition or quality of life after stereotactic radiosurgery for patients with non-small cell lung cancer with brain metastases.
What was the study design?
This was a phase III trial in which patients with 1-10 brain metastases from non-small cell lung cancer were randomised to tumour treating fields therapy following SRS or SRS alone, and were then followed with brain MR imaging every eight weeks until first intracranial progression. The primary endpoint was time to intracranial progression which was assessed by a blinded independent radiologic review committee using prespecified criteria from the validated response assessment for neuro-oncology brain metastases or brain [??].
What were the results of this study?
Tumour treating fields therapy following SRS significantly delayed time to first intracranial progression with a p-value of 0.044 and a hazard ratio of 0.72, constituting a 28% relative risk reduction that appears sustained until towards 24 months of follow-up.
Interestingly, in patients treated with immune checkpoint inhibition, tumour treating fields therapy following SRS significantly prolonged both time to first intracranial progression, with a 37% relative risk reduction, and time to distant intracranial progression, with a 59% relative risk reduction. It’s important to recognise that this benefit in intracranial progression with tumour treating fields therapy was not accompanied by any negative impact on neurocognition, health-related quality of life and safety, except for device-related grade 1-2 skin effects.
What is the clinical significance of these results, and what is next for this study?
By prolonging time to intracranial progression without causing deterioration in neurocognition or quality of life, tumour treating fields therapy following stereotactic radiosurgery is a new treatment option for patients with non-small cell lung cancer with brain metastases.
