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

138s Central Nervous System Tumors
2094^ General Poster Session (Board #19A), Sat, 1:15 PM-5:15 PM
Safety and efficacy of the addition of bevacizumab to temozolomide and
radiation therapy followed by bevacizumab, temozolomide, and irinotecan
for newly diagnosed glioblastoma multiforme. Presenting Author: James J.
Vredenburgh, Duke University Medical Center, Durham, NC
Background: Glioblastoma (GBM) has a very poor prognosis, and the
majority of patients die within 2 years of diagnosis. GBMs have high
concentrations of vascular endothelial growth factor (VEGF), and the more
VEGF, the worse the prognosis. Bevacizumab is a humanized antibody to
VEGF and is active in recurrent GBMs. The study aims to improve the
survival of newly diagnosed GBM patients by incorporating an antiangiogenic
agent with radiation and temozolomide, and adding a topoisomerase
I inhibitor, and an anti-angiogenic agent to temozolomide postradiation
therapy. Methods: Patients received standard radiation and
temozolomide at 75 mg/m2 /day, with bevacizumab at 10 mg/kg every 14
days beginning a minimum of 28 days post-operatively. Following the
completion of radiation therapy, patients received 6-12 cycles of bevacizumab,
temozolomide and irinotecan. Each cycle was 28 days. Bevacizumab
was given at a dose of 10 mg/kg days 1 and 15, temozolomide 200
mg/m2 days 1-5 and irinotecan on days 1 and 15 at 125 mg/m2 for patients
not on an enzyme inducing anti-epileptic (EIAED) and 340 mg/m2 for
patients on an EIAED. The statistical design was a goal of 60% overall
survival at 16 months. Results: 125 patients were enrolled between 8/07
and 3/09. All the patients have completed therapy. Nine patients had
thromboembolic complications (DVT or PE). Two patients had wound
dehiscence, one bowel perforation, one secondary AML and two pneumocystis
carinii pneumonias (PCP). Seventeen had grade 4 hematologic toxicity
requiring dose decrements. There were 4 toxic deaths, one each with a
myocardial infarction PCP, PE and sepsis. At a median follow-up of 40
mos, the median overall survival was 20.9 mos, the median progressionfree
survival was 13.8 mos and the 2-year overall survival was 42.4%.
Conclusions: Adding bevacizumab to temozolomide and radiation therapy
followed by bevacizumab, temozolomide with irinotecan is tolerable and
efficacious.
2096 General Poster Session (Board #19C), Sat, 1:15 PM-5:15 PM
Prognostic nomogram in elderly patients with glioblastoma. Presenting
Author: Mital Patel, Cleveland Clinic, Cleveland, OH
Background: Glioblastoma (GBM) is the most common malignant primary
brain tumor. More than half the cases occur in patients aged �65 years;
however, there is limited data on specific prognostic factors in these
patients and there is a lack of easy to use nomograms in elderly GBM
patients to provide them prognostic information. Methods: The Cleveland
Clinic Brain Tumor and Neuro-Oncology Center’s database was used to
identify elderly patients with GBM ( �65 years at the time of diagnosis).
Multivariable analysis was conducted to identify independent predictors of
survival using a Cox proportional hazards model and a stepwise selection
algorithm with p�.10 as criteria for entry and retention. �Points� were
assigned to each of these poor prognostic features and prognostic groups
were formed based on the total number of calculated points. Results: 512
GBM patients with a median age of 73 years (range 65-96, 54% male) were
included in the final analysis. On multivariable analysis six factors were
identified as having an independent impact on overall survival after
controlling for non-surgical treatment related factors like chemotherapy
and radiation: age at diagnosis (p�.0001), surgery (p� .0001), multifocal
disease (p�.0008), seizure at presentation (p�.02), hypertension (p�.05)
and Karnofsky Performance Status (p�.0001). Prognostic groups were
developed as summarized in the table. 28% of the patients had the most
favorable profile which was associated with 56% one year survival and a
13.2 months median survival. In contrast, almost all patients in the least
favorable group (27%) died within one year. Conclusions: This is an easy to
use nomogram in elderly GBM patients to provide them prognostic
information.
Prognostic groups in elderly patients (> 65 years) with glioblastoma.
Prognostic group No. of “points” 1 N (%)
1-yr survival
(%)
Median survival
(months)
Favorable 0-4 123 (28%) 56% 13.2
Intermediate 5-8 196 (45%) 19% 6.5
Unfavorable �8 117 (27%) 1% 2.8
1 Lack of seizure, HTN � 1 point; multiple tumors, age 70-79, KPS 70-80 � 2
points; biopsy only � 3 points; age �80, KPS �70 � 4 points.
2095^ General Poster Session (Board #19B), Sat, 1:15 PM-5:15 PM
Phase II study of bevacizumab plus irinotecan and carboplatin for recurrent
WHO grade 3 malignant gliomas with no prior bevacizumab failure.
Presenting Author: Annick Desjardins, Duke University Medical Center,
Durham, NC
Background: No standard treatment exists for recurrent WHO grade 3
malignant glioma patients. Bevacizumab (BV) with irinotecan has significant
anti-tumor activity for recurrent glioblastoma. Carboplatin has antiglioma
activity and can potentiate the cytotoxicity of irinotecan. We
evaluated the progression-free survival (PFS) of BV in combination to
irinotecan and carboplatin in recurrent WHO grade 3 malignant gliomas, as
well as its safety. Methods: Adult patients with measurable recurrent WHO
grade 3 malignant glioma, �12 weeks after radiation therapy, �4 weeks
after chemotherapy, with adequate organ function, KPS �70%, no prior
failure or grade �3 toxicity to the agents, and no contraindications to BV
were eligible for study. Patients received BV at 10 mg/kg with irinotecan on
days 1 and 15 of a 28-day cycle. The dose of irinotecan was 125 mg/m2 for
patients not on enzyme inducing anti-epileptics (EIAEDs) and 340 mg/m2
for patients on EIAEDs. All patients received carboplatin at an AUC of 4 on
day 1 of each cycle. MRIs were obtained every 8 weeks. Results: As
planned, 39 WHO grade III malignant glioma patients were enrolled on
study. Median age was 47 (range, 26-71). At a median follow up of 14
months, the 6-month PFS is 69% and the median PFS is 11 months. A
median of 8 cycles were given. Seven patients completed the planned
course of treatment (12 cycles) with hypometabolic PET scan and nine
patients remain on study. Fifteen patients came off study due to disease
progression and eight due to toxicity. As of 1/25/2012, 22 patients are still
alive and 17 have died. Grade 3-4 toxicities included: neutropenia (grade
3, n�12; grade 4, n� 1), thrombocytopenia (grade 3, n�6; grade 4, n�4),
nausea (grade 3, n�7), diarrhea (grade 3, n�2), deep venous thrombosis
(grade 3, n�2), febrile neutropenia (grade 3, n�1; grade 4, n�1), fatigue
(grade 3, n�8; grade 4, n�1), cerebral infarction (grade 4, n�3),
intracranial hemorrhage (grade 4, n�1), posterior reversible encephalopathy
syndrome (grade 3, n�1). Conclusions: The combination of bevacizumab,
irinotecan and carboplatin for WHO grade 3 malignant glioma
patients is effective and with no more than expected toxicity.
2097 General Poster Session (Board #19D), Sat, 1:15 PM-5:15 PM
Poor prognostic factors of post-CNS recurrence survival in breast cancer
patients. Presenting Author: Carlos Castaneda Altamirano, Instituto Nacional
de Enfermedades Neoplásicas, Lima, Peru
Background: Survival after the onset of metastases in the central nervous
system is very short. However, some variables could indicate subsets of
worse prognosis. Our aim was to determine the value of clinicopathological
characteristics and prognostic scores in the post-SNC recurrence survival.
Methods: We evaluated a retrospective cohort of 2597 breast cancer
patients treated at the Instituto Nacional de Enfermedades Neoplasicas
(Lima-Peru) between 2000-2005. Clinicopathological data was retrieved,
RPA and GPA brain metastases prognostic scores were constructed and
phenotypes were categorized according to the IHC expression in
[HR�,HER2-], [Any HR, HER2�] and Triple Negative. Survival was
calculated according to the Kaplan Meier methodology and cases were
stratified by variables evaluated. The log-rank or Breslow tests were used
when appropriate and multivariate analysis was done by the cox regression.
AP�0.05 was considered statistically significant. Results: One hundred
and fifty seven cases developed CNS metastasis, from which 23 developed
leptomeningeal metastases. The post recurrence CNS survival was 0.405
years. There were not differences according to phenotype (P�0.102),
histological grade (P�0.647), number of brain metastases (P�0.695) and
metastases volume (P�0.155). We found statistic differences in regard to
leptomeningeal carcinomatosis (present, 0.249ys vs absent 0.436ys;
P�0.033); CSF infiltration (present, 0.115ys vs absent, 1.044ys;
P�0.022); status of primary tumor (controlled, 0.501ys vs uncontrolled,
0.263ys; P�0.001); ECOG performance status (�2, 0.504ys vs �2,
0.288ys; P�0.030); and time from BC diagnosis to SNC metastases (�8
moths, 0.115 vs �8 months, 0.425ys; P�0.023). Cox regression identifies
to CSF infiltration as statistically significant (HR�9.77; P�0.025). In
regard to Prognostic scores, we found differences when cases were
stratified according to RPA score (Class I, 0.564ys vs Class II, 0.455ys vs
Class III, 0.288ys; P�0.049) and GPA score (0-1, 0.26ys vs 1.5-3,
0.455ys vs 3.5-5, 0,564; 0.048). Conclusions: RPA and GPA scores are
more accurate to identify poor survival subsets in this group of patients than
other tumor features (phenotype or histology).
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