NCOG-05. TIME TO FUNCTIONAL AND COGNITIVE DECLINE IN A PHASE 3 TRIAL OF TUMOR TREATING FIELDS WITH TEMOZOLOMIDE VERSUS TEMOZOLOMIDE ALONE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Glioblastoma is a disease characterized by progressive decline in patients’ functional status and cognitive abilities. The EF-14 phase 3 trial demonstrated that adding TTFields to temozolomide (TTFields/TMZ) compared to temozolomide alone (TMZ) led to a significant increase in both progression free survival and overall survival of patients with newly diagnosed glioblastoma who had not progressed during their initial radiation therapy with TMZ. Time dependent differences in patients’ performance status and cognitive capabilities were protocol prespecified analyses. Time to deterioration (TTD) in performance status was measured using the Kaplan-Meier method considering a sustained decrease in Karnofsky performance score (KPS) of ≥10 points or death within 90 days of the last follow up an event. Patients without decline in KPS were censored at their last evaluation. TTD in cognitive function was measured using the Kaplan-Meier method considering a sustained decrease in Mini-Mental Status Score (MMSE) of ≥6 points or death within 90 days of the last evaluation of an event. Patients with a decline in MMSE of <6 points were censored at their last evaluation. TTD in KPS was similar to time to radiological disease progression and was significantly longer in patients treated with TTFields/TMZ than with TMZ alone (median 5.5 months vs 3.9 months; HR 0.84; p=0.0092). TTD in MMSE was longer than time to deterioration in KPS in both arms, and was significantly longer in patients treated with TTFields/TMZ than with TMZ alone (median 16.7 months vs 14.2 months; HR 0.81; p=0.012). Patients with compliance ≥75% with TTFields had significantly longer TTD in MMSE (p=0.0028) but not in KPS (p=0.652) compared to patients with compliance <75%. These results suggest that decline in performance status and cognitive capabilities are correlated with disease progression and extended by the addition of TTFields to TMZ.