Erlotinib Versus Oral Etoposide in Patients With Recurrent or Refractory Pediatric Ependymoma

Duration of response (complete or partial response [CR/PR]) was defined as the time from the date of the first documented response (CR/PR) to the first documented progression or death due to underlying cancer. If a participant had not progressed or died, the duration of overall response was censored at the date of last adequate disease assessment. Duration of response was only defined for participants whose best overall response was CR or PR. Progression was defined as a worsening of neurologic status that could not be explained by other causes, a > 25% increase in tumor size, the appearance of new lesions or CSF positivity, or increasing doses of corticosteroids required to maintain stable status.

Participants with a best overall response of minor response (MR), defined as: • ≥ 25% to < 50% reduction in tumor size by bi-dimensional measurement • On a stable or decreasing dose of corticosteroids • Stable or improving neurologic examination sustained for ≥ 4 weeks.

Disease control is a best overall response of CR or PR or MR or Stable disease (SD). CR: • Complete disappearance of all enhancing tumor and mass effect • On a stable or decreasing dose of corticosteroids • Stable or improving neurologic examination sustained for ≥ 4 weeks • If CSF evaluation was positive, it must become negative (confirmed at least 2 times consecutively). PR: • ≥ 50% reduction in tumor size by bi-dimensional measurement • On a stable or decreasing dose of corticosteroids • Stable or improving neurologic examination sustained for ≥ 4 weeks. MR: • ≥ 25% to < 50% reduction in tumor size by bi-dimensional measurement • On a stable or decreasing dose of corticosteroids • Stable or improving neurologic examination sustained for ≥ 4 weeks. SD: • Neurologic examination is at least stable • Maintenance corticosteroid dose is not increased • MRI meets neither the criteria for minor response nor for progressive disease • Sustained for ≥ 8 weeks.

Progression-free survival was defined as the time from randomization to disease progression based on central nervous system (CNS)-specific evaluation criteria as assessed by the investigator or death due to any cause, whichever occurs first. Participants did not progress or die before the data cutoff date for analysis were censored at the date of last disease assessment (including both radiologic assessment and neurologic assessment) where non-progression was documented. If a participant received any further anticancer therapy without prior documentation of disease progression, the participant was censored at the date of last disease assessment before starting new anti-cancer treatment. Participants were also censored at the date of last disease assessment with no documented progression if patients discontinued treatment for undocumented progression, toxicity or other reason before the data cutoff date for analysis.

Prolonged stable disease (SD) was defined as SD with a duration of at least 16 weeks. The percentage of participants with prolonged SD was defined as participants who achieved a best overall response of CR or PR or MR or SD, and did not progress within 16 weeks from randomization. Progression was defined as a worsening of neurologic status that could not be explained by other causes, a > 25% increase in tumor size, the appearance of new lesions or CSF positivity, or increasing doses of corticosteroids required to maintain stable status.

Duration of stable disease (SD; defined as participants with an overall best response of complete, partial or minor response or stable disease) was defined as the time from the date of randomization to the first documented progression or death due to underlying cancer. If a participant had not progressed or died, the duration of SD was censored at the date of last adequate disease assessment. Duration of SD was only defined for participants whose best overall response was CR or PR or MR or SD. Progression was defined as a worsening of neurologic status that could not be explained by other causes, a > 25% increase in tumor size, the appearance of new lesions or CSF positivity, or increasing doses of corticosteroids required to maintain stable status.

Overall survival was defined as the time from the date of randomization until the documented date of death. Participants who were still alive by the data cutoff date for analysis were censored on the last day the participant was known to be alive.

An AE was defined as any untoward medical occurrence in a study participant and did not necessarily have a causal relationship with study treatment. Clinically significant vital sign assessments, findings on physical or neurological examination, and laboratory findings associated with signs and/or symptoms requiring withdrawal, dose modification or medical intervention were recorded as AEs. An AE was considered serious if it resulted in death, a life-threatening situation, inpatient hospitalization or prolongation of an existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a patient who received study drug or other important medical events. The relationship of each AE to study drug was assessed as either related or not related.

Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. Area under the plasma concentration-time curve from time zero to 24 hours (the dosing interval) measured at steady state using sparse sampling.

Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. Maximum observed plasma concentration of erlotinib (Cmax) was measured at steady state on Day 14 using sparse sampling.

Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. Time to the maximum observed plasma concentration of erlotinib (Tmax) was measured at steady state on Day 14 using sparse sampling.

Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. Apparent body clearance (CL/F) of erlotinib was measured at steady state on Day 14 using sparse sampling.

Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. The apparent volume of distribution (Vz/F) of erlotinib was measured at steady state on Day 14 using sparse sampling.