Treatment response
No patients on either stratum had an objective response to palbociclib.
A patient with anaplastic ependymoma in Stratum I was treated on a dose
of 75 mg/m2 for 18 courses before coming off therapy.
This patient was a 21 year-old male with neurofibromatosis type I and a
multiply recurrent WHO grade III anaplastic ependymoma first diagnosed
when he was 14 years-old. Prior treatment included multiple surgeries
and 2 rounds of radiation therapy. He had 7 courses of 5-fluorouracil
followed by a 1.5 year off-therapy period before starting palbociclib.
Subsequent to his progression on palbociclib, he was maintained on
additional chemotherapy regimens for 2.5 years before dying of his
tumor. A mutation profile of his tumor confirmed a C11orf95-RELA fusion
(pathognomonic of ependymoma), alterations in NF1 , and homozygous
deletion of CDKN2A and CDKN2B . He additionally had
multiple segmental chromosomal gains and losses across the genome.
Another patient with a GBM treated at 75 mg/m2 stayed
on treatment for 6 courses. In Stratum II, 3 subjects (2 at 50
mg/m2 and 1 at 75 mg/m2) remained on
treatment for 4 courses. In Stratum I and II, 16/21 (76%) and 12/13
(92%) of patients, respectively, who initiated protocol therapy
experienced disease progression while on treatment. The majority of
patients received 2 or fewer cycles of therapy (Table 5 )