Trabectedin for Recurrent Grade II/III Meningioma

Progression (PD) was measured according to the Macdonald response criteria as at least a 25% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of ≥ 5 mm. Appearance of new lesions will also constitute PD (including lesions in previously unassessed areas). Progression Free Survival (PFS) was measured from the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first. Patients without evidence of progression was censored at the last follow-up visit date. If a patient received a second anti-tumoral therapy without prior documentation of disease progression, the patient was censored at the date of starting new anti-tumoral therapy.

Time frame: From the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first up.PFS was assessed by its median the point time at which 50% of the patients have experienced disease progression or death.

Population: Per protocol population was defined as all patients who were eligible and had started their allocated treatment (at least one dose of Trabectedin or start of local standard of care therapy)

Due to the small sample size and low compliance in the Standard of Care (SoC) arm, the analysis of Quality of Life (QoL) was restricted to describing The Global health status / QoL scores at baseline. The Global health status / QoL scores are part of the EORTC QLQ-C30, which is a core questionnaire designed to assess the quality of life of cancer patients. These scores are derived from a specific scale within the EORTC Quality of Life Questionnaire (QLQ-C30) that evaluates the overall health status and quality of life of the patient. The scoring for the Global health status / QoL scale involves a linear transformation of the raw score to a standardized score ranging from 0 to 100. This scale is revised in version 3.0 of the QLQ-C30 and includes two items with a range of 6, specifically items 29 (Global health status)and 30 (QoL scale). Higher score values represent a better outcome i.e. a higher quality of life.

Time frame: Baseline measurements were collected before or on the day of the start of protocol treatment, but no earlier than 28 days before. The median baseline Global health status / QoL scores per treatment arm is reported.

Population: Safety population: all patients who had started their allocated treatment (at least one dose of Trabectedin or start of local standard of care therapy). Additionally per protocol windows were used to allocate the Qol assessments to the baseline timepoint.

Tumor response was measured according to the Macdonald response criteria as Complete Response (CR): disappearance of all target and non-target lesions. Residual lesions (other than nodes \< 10 mm) thought to be non-malignant should be further investigated before CR can be accepted. Clinical evaluation must be stable or improving. No steroids should be needed. Partial Response (PR): at least a 50% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non target lesions must be non-PD. Clinical evaluation must be stable or improving. Steroid dose must be stable or diminishing. Objective response was defined as both CR and PR. It was scheduled every 9 weeks from randomization until progression and after discontinuation of treatment without progression, every 9 weeks for the first year from randomization and every 12 weeks thereafter.

Time frame: From the date of randomization until disease progression or death, up to 24 months from date of randomization.It was assessed every 9 or 12 weeks (see measure description for details).The response rate presented is based on the best response observed.

Population: Per protocol population: all patients who were eligible and had started their allocated treatment (at least one dose of Trabectedin or start of local standard of care therapy)

Overall Survival (OS) was calculated from the date of randomization up to the date of death (any cause). For patients still alive or lost to follow-up at the time of analysis, survival will be censored at last follow-up visit date.

Time frame: From the date of randomization up to the date of death. OS was assessed by its median the point time at which 50% of the patients have experienced death.

Population: Per protocol population: all patients who were eligible and had started their allocated treatment (at least one dose of Trabectedin or start of local standard of care therapy)

The PFS probability at 6 months (PFS-6) was extracted from the Kaplan-Meyer PFS curve. 95% confidence intervals were computed based on the Greenwood's formula.

Time frame: From the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first. PFS at 6 months,the proportion of patients who have not experienced disease progression or death by 6 months is presented

Population: Per protocol population: all patients who were eligible and had started their allocated treatment (at least one dose of Trabectedin or start of local standard of care therapy)