A Phase II Study of Optune (NovoTTF) in Combination With Bevacizumab (BEV) and Temozolomide (TMZ) in Patients With Newly Diagnosed Unresectable Glioblastoma (GBM)

Twelve-month survival was determined for each subject as a binary variable indicating whether or not the subject was alive at 12 months from initiation of chemoradiation. Determination of this endpoint occurs after the subject has at least 12 months of follow-up, unless they have died sooner.

Time frame: Evaluated over 12 months

Population: The evaluable population for efficacy includes subjects who receive initial placement of the NovoTTF100A transducer arrays. Note: 4 subjects discontinued study participation prior to device placement but after initiation of RT+TMZ+BEV, and are therefore are excluded from efficacy analyses.

Duration of disease control (DoDC) was measured from the time of initiation of chemoradiation therapy until the first occurrence of either progressive disease or death. PD must be objectively determined as per RANO criteria (Updated Response Assessment Criteria for High Grade Gliomas, where PD is defined as a 25% increase in sum of products of diameters from nadir), where PD date is assessment date that identified PD. If subject died without PD, PD date was death date. For surviving subjects who didn't have documented PD, DoDC was censored at last radiologic assessment. For subjects who receive subsequent anti-cancer therapy prior to documented PD, DoDC was censored at last radiologic assessment prior to commencement of subsequent therapy. Subjects who had an initial PD event immediately following 2 or more consecutive missed assessments were censored at last assessment prior to missed assessments. DoDC was calculated only for subjects with a best overall response of SD or better.

Time frame: From date of treatment start to date of progression/death, or censored as described above; assessed for approximately 2 years.

Population: The evaluable population for efficacy includes subjects who receive initial placement of the NovoTTF100A transducer arrays. Note: 4 subjects discontinued study participation prior to device placement, and are therefore are excluded from efficacy analyses.

Duration of response (DOR) was measured from the time RANO criteria are met for CR or PR (whichever is first recorded) until the first occurrence of either progressive disease or death. PD must be objectively determined as per RANO criteria (Updated Response Assessment Criteria for High Grade Gliomas, where PD is defined as a 25% increase in sum of products of diameters from nadir), where PD date is assessment date that identified PD. If subject died without PD, PD date was death date. For surviving subjects who didn't have documented PD, DOR was censored at last radiologic assessment. For subjects who receive subsequent anti-cancer therapy prior to documented PD, DOR was censored at last radiologic assessment prior to commencement of subsequent therapy. Subjects who had an initial PD event immediately following 2 or more consecutive missed assessments were censored at last assessment prior to missed assessments. DOR was only calculated for subjects with a best response of PR or CR.

Time frame: From date of first response to date of progression/death, or censored as described above; assessed for approximately 2 years.

Population: The evaluable population for efficacy includes subjects who receive initial placement of the NovoTTF100A transducer arrays. Note: 4 subjects discontinued study participation prior to device placement, and are therefore are excluded from efficacy analyses. Duration of response was conducted specifically on those subjects in the efficacy population who achieved objective response (PR or CR).

Disease control was determined for each subject indicating whether or not they achieved an overall response of stable disease (SD) or better by RANO criteria (where a CR is indicated by disappearance of all target and non target lesions, a PR is indicated by \>= 50% decrease in sum of products of diameters of target lesions with baseline as reference, and SD is neither sufficient shrinkage to qualify for PR nor sufficient growth, \>=25%, to indicate progression).

Time frame: From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for an average of 7 months).

Population: The evaluable population for efficacy includes subjects who receive initial placement of the NovoTTF100A transducer arrays. Note: 4 subjects discontinued study participation prior to device placement, and are therefore are excluded from efficacy analyses.

Objective response was determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of complete response (CR) or partial response (PR) as determined by the Updated Response Assessment Criteria for High Grade Gliomas (RANO; where CR is indicated by disappearance of all target lesions and PR is indicated by \>=50% decrease in the sum of products of diameters of target lesions with baseline as reference). Best responses of CR or PR must be confirmed by a subsequent radiologic assessment.

Time frame: From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for an average of 7 months)

Population: The evaluable population for efficacy includes subjects who receive initial placement of the NovoTTF100A transducer arrays. Note: 4 subjects discontinued study participation prior to device placement, and are therefore are excluded from efficacy analyses.

Overall survival was defined as the duration from the initiation of chemoradiation therapy to the date of death from any cause. Subjects who were alive or lost to follow-up at the time of the analysis were be censored at the last known date they were alive.

Time frame: From date of treatment start to date of death, or censored as described above; assessed for approximately 5 years

Population: The evaluable population for efficacy includes subjects who receive initial placement of the NovoTTF100A transducer arrays. Note: 4 subjects discontinued study participation prior to device placement, and are therefore are excluded from efficacy analyses.

Progression-Free Survival (PFS) is defined as duration of time from initiation of chemoradiation therapy to first occurrence of either progressive disease (PD) or death. PD must be objectively determined as per RANO criteria (Updated Response Assessment Criteria for High Grade Gliomas, where PD is defined as a 25% increase in sum of products of diameters from nadir), where date of PD is date of assessment that identified PD. If subject died without documented PD, date of progression will be date of death. For surviving subjects who do not have documented PD, PFS will be censored at date of last radiologic assessment. For subjects who receive subsequent anti-cancer therapy prior to documented PD, PFS will be censored at the date of last radiologic assessment prior to the commencement of subsequent therapy. Subjects who have an initial PFS event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.

Time frame: From date of treatment start to date of progression/death, or censored as described above; assessed for approximately 2 years.

Population: The evaluable population for efficacy includes subjects who receive initial placement of the NovoTTF100A transducer arrays. Note: 4 subjects discontinued study participation prior to device placement, and are therefore are excluded from efficacy analyses.