No survival, QoL advantage with WBRT in metastasized NSCLC
medwireNews: Phase III trial findings suggest that whole-brain radiotherapy (WBRT) can be omitted for most non-small-cell lung cancer (NSCLC) patients with brain metastases without adversely affecting either overall survival or quality of life (QoL).
The Quality of Life after Treatment for Brain Metastases (QUARTZ) trial included 538 patients not eligible for resection or stereotactic radiation who were randomly assigned to receive best supportive care (BSC), including dexamethasone, either with or without 20 Gy WBRT administered in five daily fractions.
As the primary outcome measure, researcher Ruth Langley (University College London, UK) and team chose quality-adjusted life–years (QALYs), which combines overall survival and QoL, as assessed by the weekly completion of the patient-reported EuroQol EQ-5D 3L questionnaire.
The average QALY was 46.4 days for WBRT-treated participants and 41.7 days for those who did not receive WBRT, equating to a difference of 4.7 days, which was within the noninferiority margin of 7 days.
Taken separately, overall survival did not differ significantly between treatment arms, at a median of 9.2 weeks for the WBRT group and 8.5 weeks for the BSC group.
And similarly, QoL was also comparable across groups at weeks 4, 8 and 12 post-randomisation, the researchers report in The Lancet.
Furthermore, during the initial 8 weeks after randomisation, a similar proportion of participants in the WBRT and BSC arms underwent a dexamethasone dose reduction, a finding that “challenges the dogma that WBRT can be seen as a potential steroid-sparing modality”, they say.
Patients given WBRT were significantly more likely to experience drowsiness, alopecia, nausea and scalp discomfort at week 4 than BSC-treated participants. But the incidence of serious adverse events was similar across arms.
The QUARTZ investigators conclude: “The combined evidence suggests that WBRT offers no substantial benefit to most patients with brain metastases from NSCLC in terms of improved survival, overall quality of life, or reduction in steroid use.”
However, subgroup analysis showed a significant association between treatment group and age, such that younger patients, especially those aged less than 60 years, derived an overall survival benefit with WBRT. And there were trends for improved survival in patients with a Karnofsky performance status (KPS) of 70 or higher and those with controlled primary NSCLC.
Commentator Cécile Le Pechoux (Gustave Roussy Cancer Campus, Villejuif, France) and co-authors note that the “results of this trial emphasise the robustness of prognostic factors such as age and KPS”, adding that “[i]t now seems clear that an elderly patient, with a KPS of less than 70 and uncontrolled primary, should not have WBRT.”
However, they continue: “[W]e believe that optimised WBRT, given at the right time to appropriate patients, could lead to more individualised strategies. Both systemic and local treatments of brain metastases need to be discussed with patients, taking into account the results of this trial, classic prognostic factors, and the molecular status.”
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