Which endpoint was put first
SWOG S1827 MAVERICK compared brain MRI surveillance alone with the same surveillance plus prophylactic cranial irradiation (25 Gy in 10 fractions) in limited- or extensive-stage small-cell lung cancer. Initial therapy had finished; MRI before entry showed no brain metastases. Both arms had brain MRIs every three months in the first year and every six months in the second, with the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association and Trail Making Test at the same intervals.[1]
Median follow-up among living people was 22 months. The primary endpoint was cognitive failure-free survival: MRI alone reduced the risk of cognitive failure or death by 40% (HR 0.60; 90% interval 0.46-0.78; p=0.001). Grade 3-5 adverse events were 0.8% versus 7.9%, with one grade 5 encephalopathy event in the MRI-plus-irradiation arm. The presentation was given at a conference.[1]
The survival comparison has not closed
A preliminary overall survival analysis after 128 deaths showed no apparent difference (HR for MRI alone 0.90; 90% interval 0.67-1.20). The final analysis is planned after 190 deaths. Brain metastasis-free survival was not significantly different (HR 1.25; 90% interval 0.95-1.66). The presenter said the results support MRI surveillance alone as the standard of care. What the primary endpoint licenses is this composite of cognitive failure or death; the 90% interval also shows how that composite was tested. The signal to watch once 190 deaths have accrued is whether the MRI-alone overall survival curve falls behind the irradiation arm.[1]