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

140s Central Nervous System Tumors
2102 General Poster Session (Board #20A), Sat, 1:15 PM-5:15 PM
Correlation between CD4 lymphocytes count and the opportunistic infections
in treated glioblastoma. Presenting Author: Marie Josee Begin,
University of Montreal, Montreal, QC, Canada
Background: Less than 200 CD4 lymphocytopenia happens frequently with
temozolomide treatment of glioblastoma. This immunosuppression is
associated with many opportunistic infections and antibiotic prophylaxis is
given in some centers to prevent Pneumocystis pneumonia. Methods: We
analyzed the association between documented culture-proved infections
and CD4 lymphocytes level in 140 patients treated with temozolomide in
first-line glioblastoma in Notre-Dame Hospital from 2006 to 2009.
Demographic and treatment data were collected and analyzed with Kaplan-
Meier survival plots and Log Rank tests. Results: The cohort of infected
patients was represented by 31 patients who developed 49 culture-proved
infections: 21 urinary origin, 8 pulmonary (1 Pneumocytis and 2 Aspergillosis),
5 brain, 5 bacteremia and 2 other. The infected cohort (n�31) had
similar demographs, but also similar outcome compared to our control non
infected glioblastoma treated patients cohort (n�109) with a 2 year
survival of 40.8% vs 50.2% (p�). The median CD4 lymphocytes level was
260, but clearly infections were associated with less than 200 CD4
lymphocytes. During their infection, 20 patients had a CD4 level less than
200, compared with 11 patients with more than 200 CD4 lymphocytes
count. Conclusions: CD4 lymphocytopenia less than 200 is associated with
increase in number of documented culture-proven infections in patients
treated with temozolomide, but the survival is not altered by the infection.
TPS2104 General Poster Session (Board #20C), Sat, 1:15 PM-5:15 PM
A phase III randomized controlled trial of short-course radiotherapy with or
without concomitant and adjuvant temozolomide in elderly patients with
glioblastoma (NCIC CTG CE.6, EORTC 26062-22061, TROG 08.02,
NCT00482677). Presenting Author: James R. Perry, Sunnybrook Health
Sciences Centre, Toronto, ON, Canada
Background: The EORTC (26981-22981)/NCIC CTG (CE.3) RCT in newly
diagnosed GBM found improved survival with concomitant and adjuvant
temozolomide (TMZ) added to radiotherapy (RT). Study pts were 18-71
(median 56) years; however a sub-group analysis noted a trend of
decreasing benefit from the addition of TMZ with increasing age, such that
for age 65-71, the hazard ratio of 0.8 did not reach statistical significance
(p�0.340). Recent RCTs in elderly GBM found improved survival with RT
compared to supportive care alone and detected non-inferiority of 40 Gy/15
vs. a 60 Gy/30 RT regimen. Based upon these results short-course
hypofractionated RT is often recommended for elderly pts. However,
whether the addition of TMZ to RT confers a survival advantage in elderly
pts remains unanswered. Methods: Patients �65 yrs of age with histologically
confirmed newly diagnosed glioblastoma, ECOG 0-2, are randomized
1:1 to receive 40Gy/15 RT vs. 40Gy/15 RT with 3 weeks of concomitant
temozolomide plus monthly adjuvant TMZ until progression or 12 cycles.
Stratification is by centre, age (65-70, 71-75, or 76�), ECOG 0,1 vs 2, and
biopsy vs resection. For 90% power to detect a 25% reduction in the
primary outcome of overall survival (increased MST from 6 to 8 months)
between arms, using a two-sided 5% alpha, a minimum of 520 deaths
must be observed prior to analysis; total sample size is 560 patients. The
trial is open in Canada (NCIC CTG), Europe (EORTC), Australia and New
Zealand (TROG), and Japan. As of Jan 25, 2012, 361 (65%) of the target
560 pts were randomized (147 Canada, 144 Europe, 64 Australasia, 6
Japan). Median age of randomized patients is 73 (65-88) years. A planned
futility analysis after 120 events by the independent DSMB resulted in a
recommendation that the trial continue.Accrual is expected to be complete
in 2013. A comprehensive molecular companion analysis, including
MGMT promoter methylation, is planned.
TPS2103 General Poster Session (Board #20B), Sat, 1:15 PM-5:15 PM
REACT: A phase II study of rindopepimut (CDX-110) plus bevacizumab
(BV) in relapsed glioblastoma (GB). Presenting Author: David A. Reardon,
Dana-Farber Cancer Institute, Boston, MA
Background: EGFRvIII is a constitutively active tumorigenic deletion mutation
of EGFR. It is expressed in ~30% of primary GB where it is linked to
poor long-term survival (Pelloski 2007). The investigational vaccine rindopepimut
consists of the unique EGFRvIII peptide sequence conjugated to
keyhole limpet hemocyanin (KLH), delivered intradermally (500ug with
150ug GM-CSF as an adjuvant). Remarkably consistent and promising
results across 3 phase II studies in newly diagnosed, resected EGFRvIII�
GB (Lai 2011) represent a statistically significant improvement over a
historical control cohort matched for major eligibility criteria (median
overall survival [OS] � 24.4 - 24.6 vs. 15.2 months from diagnosis [m] and
median progression-free survival [PFS] � 12.3 - 15.3 vs. 6.4 m). ACT IV, a
phase III trial in this population, is ongoing. The immunosuppressive
influence of residual/advanced GB presents a challenge to activation of
efficacious antitumor immune responses. Anecdotal evidence (compassionate
use cases, Sampson 2008) suggests that rindopepimut may induce
specific immune responses and regression in multifocal and bulky residual
tumors. Rindopepimut with BV, which inhibits VEGF and its immunosuppressive
properties (including impaired maturation of dendritic cells and
disruption of tumoral T cell infiltration [Johnson 2007, Shrimali 2010])
may further optimize EGFRvIII-specific immune response and antitumor
activity. Methods: ReACT is a Phase II study of rindopepimut plus BV in
patients (pts) with 1st or 2nd relapse of EGFRvIII� GB. BV-naïve pts will be
enrolled to Group 1 (n�70: randomized 1:1 to BV plus either rindopepimut/
GM-CSF or control injection [low-dose KLH]) while BV-refractory patients
will enter Group 2 (n�25: to receive BV plus open-label rindopepimut/GM-
CSF). Concurrent with BV (10 mg/kg, q 2 wks), blinded treatment or
open-label vaccine is given in priming phase (days 1, 15 and 29), then
monthly until PD. Tumor response is assessed every 8 weeks, and patients
are followed for survival after PD. Objectives are PFS at 6 months (primary),
objective response rate, PFS, OS, safety, immunogenicity and elimination
of EGFRvIII. ReACT opened to accrual in December 2011 (NCT01498328).
TPS2105 General Poster Session (Board #20D), Sat, 1:15 PM-5:15 PM
Bevacizumab plus radiotherapy for elderly patients with glioblastoma
(ARTE). Presenting Author: Ghazaleh Tabatabai, Department of Neurology,
University Hospital Zurich, Zurich, Switzerland
Background: The standard of care for patients with newly diagnosed
glioblastomas after surgical resection is radiotherapy with concomitant and
adjuvant temozolomide chemotherapy. Yet, inclusion into the pivotal trial
was limited to patients up to the age of 70, and subgroup analyses
suggested that older patients did not gain benefit from combined modality
treatment. Further, the efficacy of radiotherapy has been confirmed in a
randomized trial comparing best supportive care versus radiotherapy alone.
Of note, hypofractionated radiotherapy is equieffective in patients aged
65-70 years and more. Two randomized trials in elderly patients (NOA-08,
Nordic Trial) indicated smilar efficacy of primary temozolomide chemotherapy
alone compared with radiotherapy alone. Combined radiochemotherapy
is compared with radiotherapy alone in an ongoing NCIC-CTG
EORTC TROG Japanese group trial 26062-22061. Thus, radiotherapy
alone is the standard of care for newly diagnosed glioblastoma of elderly
patients. These clinical data justify the exploration of new, temozolomidefree
first-line treatment strategies in elderly patients. Methods: The ARTE
trial will therefore investigate bevacizumab when added to a short course of
radiotherapy and bevacizumab maintenance therapy until progression. The
translational research program shall include blood and urine biomarker
analysis and FET-PET in addition to MRI for monitoring the course of the
disease. This trial is an explorative randomized, non-comparative phase II
trial aiming at recruiting 60 patients in Switzerland. Elderly patients (� 65)
will be randomized 2:1 either to the experimental arm (bevacizumab plus
radiotherapy) or the standard arm (radiotherapy). The primary endpoint is
median overall survival. Secondary endpoints include overall survival at 6
months, overall survival at 12 months, median progression-free survival,
progression-free survival at 6 months, median time to treatment failure.
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