Annual Meeting Proceedings Part 1 - American Society of Clinical ...

128s Central Nervous System Tumors
2051 General Poster Session (Board #13F), Sat, 1:15 PM-5:15 PM
Phase II study of PX-866 in recurrent glioblastoma. Presenting Author:
Marshall W. Pitz, CancerCare Manitoba, University of Manitoba, Winnipeg,
MB, Canada
Background: Glioblastoma (GBM) is the most aggressive malignancy of the
central nervous system. The majority of GBM have genetic changes that
increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal
transduction pathway, critical for cell motility, proliferation, and survival.
We present the interim results of PX-866, an oral PI3K inhibitor, in patients
(pts) with recurrent GBM. Methods: Pts with histologically confirmed GBM
at first recurrence after treatment with chemoradiation and adjuvant
temozolomide are given PX-866 8 mg daily on this single-arm phase II
study. MRI and clinical exam are done every 8 weeks to determine
treatment response. The trial has a 2-stage design with dual endpoints of
objective response and early progression (within 8 weeks). In Stage I, 15
pts are evaluated and if 0 responses and 10 or more early progressions are
seen, enrolment will stop. Otherwise, Stage II will enrol another 15 pts for
efficacy analysis. Tumour tissue is collected for analysis of potential
markers of PI3K inhibitory activity (PTEN, EGFRvIII, PIK3CA mutations).
Results: Seventeen pts have been enroled to date: 14 evaluable for response
and 15 for toxicity. Median age was 54 years (range 35-70), with 7 females
and 10 males. No pts had received treatment for recurrent GBM, and
median time between initial diagnosis and study enrolment was 300 days
(range: 113-447 days). Pts have received a median of one 8-week cycle of
PX-866 (range: 1-4). Twelve pts have discontinued therapy, 9 due to
disease progression and 3 due to grade 3/4 liver enzyme abnormalities.
Other adverse effects have included fatigue (10 pts/1 grade 3), diarrhea (6
pts/3 grade 3), nausea (7 pts/0 grade 3), vomiting (6 pts/0 grade 3),
lymphopenia (14 pts/3 grade 3). Stage I response data are premature; it is
not yet known if the trial will continue to Stage II. Archival tissue is
available on all patients and is undergoing analysis. Conclusions: This is one
of the first trials of a PI3K inhibitor in pts with recurrent GBM. PX-866 has
been relatively well tolerated. Stage I response data are premature; while it
is not yet known if the criteria will be met to continue to Stage II, prolonged
SD has been observed in some pts. The correlative biomarker assays
underway will be important to understand this observation.
2053 General Poster Session (Board #13H), Sat, 1:15 PM-5:15 PM
Correlation of large brain edema with favorable prognosis in patients with
single brain metastases. Presenting Author: Matthias Preusser, Department
of Medicine I and Comprehensive Cancer Center CNS Tumours Unit,
Medical University of Vienna, Austria, Vienna, Austria
Background: The sub-cohort of brain metastases (BM) patients (pts) with
single BM has relatively favorable survival times, but novel prognostic
factors are needed to individualize patient management. Methods: We
retrospectively evaluated pre-operative magnetic resonance images in
patients, who underwent neurosurgical resection of a single BM. The
localization and largest diameter of the BM was recorded. The extent of
brain edema (BE) was graded on contrast-enhanced T1, T2 and fluidattenuated
inversion recovery (FLAIR) images as follows: BE �1cm, BE �1
cm without affection of the contralateral hemisphere, BE �1cm with
affection of the contralateral hemisphere. Further, immunohistochemically
assessed expression of hypoxia-induced factor 1 alpha (HIF1a) was
analyzed in each BM tissue specimen. Results: 159 pts were studied (81
male, 78 female; age range 24 to 80 years, median 58). The primary
tumors were lung carcinoma in 74, breast cancer in 26, kidney cancer in
13, colorectal cancer in 11, melanoma in 9 and other tumor types in 26
cases. At univariate analysis, we found a significant positive correlation of
overall survival time (OS) with young age, Karnofsky index �80, nonmelanoma
histology, and, surprisingly, large BE (p�0.05, log-rank test). At
multivariate analysis, pts age, histological diagnosis and extent of BE
remained independent prognostic parameters (Cox regression model,
p�0.05). We found a significant positive correlation of extent of BE with
expression of HIF1a (Mann-Whitney-U test, p�0.003). Conclusions: Large
BE positively and independently correlates with favorable prognosis in pts
operated for single BM. Peritumoral BE correlates with HIF1a expression,
indicating a possible role of tumor hypoxia in its formation.
Parameter n
Median
OS/days
(95% CI)
p value
(univariate)
p value
(multivariate)
Age � 60 years 90 435 (334-536) 0.02 0.014
�60 years 69 263(121-405)
Karnofsky index �80 29 179 (37-321) 0.047 0.242
�80 110 443(344-542)
Histological diagnosis Non-melanoma 150 423 (329-517) �0.001 �0.001
Melanoma 9 130 (95-165)
Extent of BE �1cm 26 209(137-281) 0.004 0.008
�1cm, only ipsilateral
hemisphere
105 435 (334-536)
�1cm, ipsi- and
contralateral hemisphere
28 575 (235-915)
2052 General Poster Session (Board #13G), Sat, 1:15 PM-5:15 PM
Concurrent intrathecal methotrexate and liposomal cytarabine for the
treatment of leptomeningeal metastasis from solid tumors. Presenting
Author: Brian J. Scott, University of California, San Francisco, San
Francisco, CA
Background: Leptomeningeal metastasis (LM) from solid tumors is typically
a late manifestation of disease with a median survival of weeks to a few
months. Treatment is palliative, with no widely accepted standard of care.
Options include intrathecal (IT) or systemic chemotherapy, radiation
therapy or ventriculoperitoneal shunting. Randomized trials comparing
single agent IT methotrexate to liposomal cytarabine have shown similar
efficacy and tolerability. There is limited data, however, on the use of
combination IT chemotherapy in solid tumor LM. Methods: We conducted a
retrospective cohort study of 19 subjects treated for LM from solid tumors
at a single institution. In addition to therapies directed at active solid tumor
sites, each subject received IT liposomal cytarabine plus IT methotrexate
injections every two weeks. Survival data and treatment-related toxicities
were determined by systematic chart review. Results: LM was diagnosed by
CSF cytology in 12/19 (63%), while the remainder were diagnosed by
clinical and MRI findings. The most common cancer types were breast
7(37%), glioblastoma 6(32%) and lung 3(16%). The majority 18(95%)
had active systemic or parenchymal brain disease at the time of treatment,
requiring systemic chemotherapy 18(95%) or radiation therapy 13(68%).
The median number of IT treatments was 4(range 1-9). Treatment was
interrupted due to toxicity in 3(17%), while 7(37%) experienced � CTCAE
grade III toxicities, most commonly meningitis 3(16%). Treatment was
stopped in 7/19(37%) following complete cytologic response 6/11(55%)
or radiographic clearance 1/7(14%). The median overall survival was 96
days(n�6; range 29-158), median time to neurologic progression was 46
days (n�9; range 6-101) and the most common cause of death was
progression of systemic disease 4(67%). Conclusions: Combination IT
chemotherapy was reasonably well-tolerated, even in a population also
receiving chemotherapy for progressive systemic disease. IT-related adverse
events occurred at rates similar to previously reported single agent
trials. Prospective evaluation is necessary to determine whether there is a
survival benefit compared to single agent IT chemotherapy.
2054 General Poster Session (Board #14A), Sat, 1:15 PM-5:15 PM
Management of primary intraocular lymphoma (PIOL): Results from the
prospective German PIOL registry (PIOL-R). Presenting Author: Kristoph
Jahnke, Hematology and Oncology, Charité Campus Benjamin Franklin,
Berlin, Germany
Background: Primary intraocular lymphoma (PIOL) is a very rare disorder,
and the optimal treatment is yet to be defined. Here, we report clinical
characteristics and outcome of patients with PIOL enrolled in the prospective
German PIOL registry (PIOL-R). Methods: Patient data in this prospective,
non-interventional multicenter study were compiled by standardized
questionnaires sent to Ophthalmology and Hematology/Oncology centers in
Germany. All histologically or cytologically confirmed immunocompetent
PIOL patients were eligible. Results: Fifteen patients (8 female, median age
66 years, median Karnofsky performance status 90%) from 4 centers were
included between August 2008 and January 2012. Median follow-up was 7
months. Median time from first occurrence of symptoms to PIOL diagnosis
was 5 (range, 1-11) months. All PIOL were of diffuse large B-cell histology.
Eight patients had concomitant (n�3), prior (n�2) and/or subsequent
(n�4) parenchymal brain involvement. First-line treatment included methotrexate
(MTX)-, rituximab- and/or ifosfamide-based systemic chemotherapy
in 12 (including high-dose chemotherapy [HDCT] with autologous stem cell
transplantation [ASCT] in 2), intraocular (i.o.) chemotherapy with MTX
(n�2) and/or rituximab (n�6) in 7, and ocular radiation in one patient(s).
Two patients received prophylactic intrathecal (i.th.) treatment with MTX
and none had whole-brain irradiation. The PIOL remission rate was 100%
(complete remission in 11/14 evaluable patients and partial remission in 3
patients). Four patients relapsed in the brain after 5, 6, 21 and 23 months
and received salvage treatment with MTX and/or ifosfamide (n�3) and
HDCT with ASCT (n�1). No ocular or systemic relapses were observed.
Median progression-free survival was 23 (95% confidence interval, 19-26)
months. All patients are alive. Conclusions: Although the awareness of PIOL
and diagnostic possibilities have improved over the past 2 decades, time
from symptom presentation to diagnosis seems to remain at previously
reported levels. There appears to be a shift from local ocular treatments and
radiation to systemic therapy as compared to anecdotal data with promising
response and survival rates.
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