According to results of a phase 3 clinical trial published in the Lancet, whole brain radiotherapy (WBRT) does not improve quality of life of (QOL), or survival benefit for, patients with non-small cell lung cancer (NSCLC) that has spread to the brain.1 WBRT and dexamethasone are widely prescribed to treat brain metastases from NSCLC, despite a lack of randomized clinical trials showing that WBRT is not beneficial, though it is linked to many adverse events.
“Clinicians now have robust evidence that will help inform discussions with patients with NSCLC and brain metastases not suitable for surgery or stereotactic radiosurgery,” said study co-author Paula Mulvenna, a consultant clinical oncologist at the Newcastle Hospitals NHS Foundation Trust in the United Kingdom, in an email to Cancer Therapy Advisor. “Systemic anti-cancer treatment options should continue to be explored where possible if the patient is well enough. These patients should no longer be excluded from future clinical trials.”
In the Quality of Life after Treatment for Brain Metastases (QUARTZ) trial, Dr Mulvenna and colleagues enrolled 538 patients with brain- metastatic NSCLC. Patients were randomly assigned to receive either WBRT plus dexamethasone or best supportive care plus dexamethasone.
The primary outcome was quality-adjusted life years (QALY), which combines quality and length of life. The difference between average QALYs was 4.7 days. There was no evidence of difference in overall survival, overall QOL, or dexamethasone-use between the 2 groups.
The study authors contend that their findings should affect treatment guidelines for this patient population.
“The QUARTZ trial gives strong evidence to support amendments to treatment guidelines,” said Dr Mulvenna. “By showing that whole brain radiotherapy can be safely omitted for patients with brain metastases not suitable for surgery or stereotactic radiotherapy, it is clear we should no longer consider it to be the standard comparator for future trials for these patients.”
In an accompanying comment, Cécile Le Pechoux of the Gustave Roussy Cancer Campus in Villejuif, France, and colleagues praised the trial as “well designed.” But they also argued that the trial does not necessarily rule out WBRT for all patients with NSCLC and brain metastases. The authors claim that WBRT could still lead to individualized treatment if it is “given at the right time to appropriate patients,” and that the trial’s results should be taken into account in treatment discussions with patients.2
Dr Mulvenna said that while she agreed that the trial provides a “firmer foundation” for treatment discussions, the use of WBRT should be weighed against the treatment’s toxicity and the fact that QOL is not significantly improved even among those younger patients who saw a 3-week survival benefit.
“Researchers may wish to continue optimizing whole brain radiotherapy, with hippocampal sparing techniques, in younger patient groups,” she said. “In those over 60 years old, however, the QUARTZ trial confirms that whole brain radiotherapy does not provide the benefit we had aimed for.”
Dr Mulvenna and her colleagues are analyzing additional data on QOL and the impact of WBRT on the careers of patients who took part in the QUARTZ trial. They are also eager to promote the inclusion of patients with brain metastases in future clinical trials.
- Mulvenna P, Nankivell M, Barton R, et al. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. The Lancet. 2016 September 4. doi: 10.1016/ S0140-6736(16)30825-X [Epub ahead of print]
- Le Pechoux C, Dhermain F, Besse B. Whole brain radiotherapy in patients with NSCLC and brain metastases. The Lancet. 2016 September 4. doi: 10.1016/ S0140-6736(16)31391-5 [Epub ahead of print]