TAMI-19. IMMUNOHISTOLOGICAL ANALYSIS OF ANGIOGENIC FACTORS OTHER THAN VEGF IN GLIOBLASTOMAS IN RELATION TO THE USE OF BEVACIZUMAB

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi202-vi202
Author(s):  
Taketo Ezaki ◽  
Ryota Tamura ◽  
Toshihide Tanaka ◽  
Yuki Kuranari ◽  
Keisuke Miyake ◽  
...  
Keyword(s):  
Growth Factor ◽  
Performance Status ◽  
Progression Free Survival ◽  
Angiogenic Factors ◽  
In Situ Observation ◽  
Newly Diagnosed ◽  
Naive Group ◽  
Paired Samples ◽  
Initial Surgery ◽  
Effective Group

Abstract Although bevacizumab was shown to improve progression-free survival and performance status of the patients with high-grade gliomas, clinical trials consistently showed lack of benefit in terms of patients’ overall survival. The recurrent tumors are inevitably more aggressive and invasive as compared with the original tumors, and the in-situ observation in actual human specimens is essential to elucidate the mechanism of resistance. In Japan, bevacizumab was approved not only for recurrent but also for newly diagnosed cases. The safety as well as efficacy of resection following neoadjuvant bevacizumab has been reported, and a phase II study is currently ongoing (UMIN-000025579). In the present study, the expression of angiogenic factors other than VEGF (basic fibroblast growth factor (bFGF), placenral growth factor (PlGF), angiopoietin1/2 and ephrinA2) was investigated by immunohistochemistry to be compared among tumors with no previous bevacizumab treatment, those resected following bevacizumab, and those refractory to bevacizumab. Fifty-nine samples from 42 patients were included; 24 of newly diagnosed glioblastomas with no previous bevacizumab (naïve group), 16 resected following neoadjuvant bevacizumab (effective group), and 6 resected after recurrence or autopsied (refractory/autopsied group). 12 were paired samples (8 naïve and refractory, 4 effective and refractory). The expression of PlGF significantly increased in the effective group as compared with the naïve group (p=0.003). In the paired specimens, there was a trend towards increased expression of PlGF in the second specimens (refractory/autopsied group) as compared with the specimens of initial surgery (p=0.083). Angiopoietin1, angiopoietin2 and ephrinA2 were characteristically expressed in the microvessels less than 15μm. The increased expression of PlGF might be associated with the recurrence after bevacizumab.

Addition of temozolomide to radiotherapy for treatment of newly diagnosed anaplastic gliomas

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13037-e13037
Author(s):  
M. Simonelli ◽  
G. Banna ◽  
P. Navarria ◽  
A. Di Ieva ◽  
P. Zucali ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Tumor Biopsy ◽  
Initial Surgery ◽  
Anaplastic Gliomas ◽  
Oligodendroglial Component ◽  
Histological Heterogeneity ◽  
Radio Sensitivity

e13037 Background: Anaplastic astrocytoma (AA), oligodendroglioma (AOD), and oligoastrocytoma (AOA) are rare tumors showing variable outcome due to their histological heterogeneity and different chemo- and radio-sensitivity. The presence of an oligodendroglial component is associated with LOH 1p/19 and a prolonged survival. Currently, the addition of chemotherapy to radiotherapy (RT) for newly diagnosed anaplastic gliomas is not sustained by available data. We evaluated the addition of temozolomide (TMZ) to radiotherapy for newly diagnosed anaplastic gliomas in terms of tolerability, progression-free survival (PFS), and overall survival (OS). Methods: Since September 2004, following initial surgery, patients (pts) with histologically confirmed anaplastic glioma, Karnofsky Performance Status (KPS) ≥40, adequate organ function, no prior chemotherapy, were treated with RT to limited fields once daily at 2 Gy per fraction, 5 days a week, for a total of 60 Gy with concomitant TMZ (75 mg/m2 for 7 days a week) followed by 6 cycles of maintenance TMZ at 200 mg/m2 on days 1–5 every 28 days. LOH 1p/19q was assessed by fluorescence in situ hybridization (FISH). Results: Twenty-eight pts were treated, 20 males, 8 females, median age 51 (range, 22–75), median KPS 90 (range, 40–100). Eleven pts had AOD (39%), 10 AA (36%), 6 AOA (21%), 1 pt gliosarcoma (4%). Nine pts (32%) underwent tumor complete resection, 10 partial resection (36%), and 9 (32%) tumor biopsy. In 1 patient with AOD RT and concomitant TMZ were interrupted at 44 Gy because of cerebral oedema, while in 1 patient with AA maintenance TMZ was suspended due to cumulative myelosuppression. Other severe toxicities included one spondilodiscitis, and a cutaneous G3 rush. Frequent mild toxicities were grade 1–2 nausea/vomiting (17 pts-63%), and grade 1–2 asthenia (8 pts-30%). With a median follow-up of 18 months (range, 4–53), median PFS, and 1-year PFS were 14.8 months and 72.6%, respectively; 1-year OS was 84.3%, median OS was not reached yet. Data on LOH 1p-19q available on 16 pts will be presented. Conclusions: The addition of temozolomide to radiation therapy for newly diagnosed anaplastic gliomas is well tolerated and seems active; efficacy needs confirmation in a randomized clinical trial. No significant financial relationships to disclose.

Tissue plasminogen activator in chronic subdural hematomas as a predictor of recurrence

2006 ◽  
Vol 104 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Hiroyuki Katano ◽  
Ken Kamiya ◽  
Mitsuhito Mase ◽  
Motoki Tanikawa ◽  
Kazuo Yamada
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Venous Blood ◽  
Angiogenic Factors ◽  
Subdural Hematomas ◽  
Initial Surgery ◽  
Significant Difference ◽  
Tissue Plasminogen ◽  
Endothelial Growth Factor

Object Chronic subdural hematomas (CSDHs) recur in 7 to 18% of cases. The present study was conducted to determine whether serum or lesion concentrations of coagulofibrinolytic and angiogenic factors, which have been reported to be potential markers of CSDH development, might predict such recurrences. Methods Sixty consecutive patients (mean age 71.5 years) with CSDHs (74 affected sides) were studied. Samples of serum in preoperative peripheral venous blood and of hematomas (obtained during surgery) were collected and analyzed. The CSDH recurred in six (8.1%) of the 74 affected sides in six patients. None of the values of the coagulative factors or tests in serum showed significant variation between cases with and those without recurrence. Among coagulofibrinolytic factors, tissue plasminogen activator (TPA) in hematomas demonstrated significantly greater levels in recurrent than in nonrecurrent cases; a similar tendency was noted for α2-plasmin inhibitor–plasmin complex in hematomas. Both factors were greater in the lesions than in the serum. Among the angiogenic factors, levels of hepatic growth factor (HGF) and vascular endothelial growth factor (VEGF) in hematomas were significantly greater than in serum, whereas those of basic fibroblast growth factor were rather lower. Note that comparisons between recurrent and nonrecurrent cases revealed no significant difference. Conclusions Patients harboring CSDHs with high TPA concentrations on sampling at the initial surgery have a relatively high probability of recurrence and require follow up with computerized tomography scanning. Angiogenic factors, such as HGF and VEGF, might be candidate markers of CSDH enlargement but are not useful as predictors of recurrence.

Expression pattern and prognostic significance of myosin light chain 9 (MYL9): a novel biomarker in glioblastoma

2019 ◽  
Vol 72 (10) ◽  
pp. 677-681 ◽  
Author(s):  
Banavathy S Kruthika ◽  
Harsha Sugur ◽  
Kanuri Nandaki ◽  
Arivazhagan Arimappamagan ◽  
Kondaiah Paturu ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Newly Diagnosed ◽  
Paired Samples ◽  
Idh1 R132h ◽  
Recurrent Gbm

AimsTumour recurrence is inevitable in glioblastoma (GBM) and mostly noted in the peritumoural brain zone (PT). In our previous microarray-based study, we identified Myosin Light Chain 9 (MYL9) as a highly expressed gene in the PT of GBM. Therefore, we aimed to study the expression pattern and clinical significance of MYL9 in GBM.MethodsPatient samples included three retrospective cohorts: 25 GBM cases with differential biopsies of tumour core and PT, 62 retrospective cases of newly diagnosed GBM with survival information and 20 paired samples (newly diagnosed and recurrent GBM). All tumour tissues, archived as formalin fixed paraffin embedded blocks were retrieved and immunohistochemistry for MYL9 and IDH1 R132H was performed. MYL9 expression was correlated with patient prognosis in our cohort and in The Cancer Genome Atlas (TCGA) and Rembrandt cohorts. It was further evaluated in the 20 paired samples of GBM.ResultsMYL9 showed a cytoplasmic membranous staining of tumour cells. The staining pattern was variable and patchy within tumours. Higher MYL9 expression was associated with poor overall and progression-free survival in our and in TCGA and Rembrandt cohorts. The expression of MYL9 was higher in IDH1 R132H immunonegative cases.ConclusionsWe show MYL9 as a novel biomarker, variably expressed in GBM. The association of high MYL9 expression with poor prognosis in newly diagnosed GBM patients and increased expression in recurrent GBM is indicative of its role in conferring tumour aggressiveness.

scholarly journals Immunologic Escape After Prolonged Progression-Free Survival With Epidermal Growth Factor Receptor Variant III Peptide Vaccination in Patients With Newly Diagnosed Glioblastoma

2010 ◽  
Vol 28 (31) ◽  
pp. 4722-4729 ◽  
Author(s):  
John H. Sampson ◽  
Amy B. Heimberger ◽  
Gary E. Archer ◽  
Kenneth D. Aldape ◽  
Allan H. Friedman ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Delayed Type Hypersensitivity ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Epidermal Growth

Purpose Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed in normal tissues but widely expressed in glioblastoma multiforme (GBM) and other neoplasms. Patients and Methods A phase II, multicenter trial was undertaken to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival (PFS) and overall survival (OS) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease. Intradermal vaccinations were given until toxicity or tumor progression was observed. Sample size was calculated to differentiate between PFS rates of 20% and 40% 6 months after vaccination. Results There were no symptomatic autoimmune reactions. The 6-month PFS rate after vaccination was 67% (95% CI, 40% to 83%) and after diagnosis was 94% (95% CI, 67% to 99%; n = 18). The median OS was 26.0 months (95% CI, 21.0 to 47.7 months). After adjustment for age and Karnofsky performance status, the OS of vaccinated patients was greater than that observed in a control group matched for eligibility criteria, prognostic factors, and temozolomide treatment (hazard ratio, 5.3; P = .0013; n = 17). The development of specific antibody (P = .025) or delayed-type hypersensitivity (P = .03) responses to EGFRvIII had a significant effect on OS. At recurrence, 82% (95% CI, 48% to 97%) of patients had lost EGFRvIII expression (P < .001). Conclusion EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III, randomized trial.

scholarly journals P14.31 CMV reactivation in a cohort of newly-diagnosed glioblastoma patients treated with temozolomide chemoradiotherapy. A single center analysis

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii73-iii74
Author(s):  
R URSU ◽  
J Doridam ◽  
E Chaugne ◽  
H Zannou ◽  
C Belin ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Single Center ◽  
Positive Serology ◽  
Cd4 Lymphocyte ◽  
Cmv Reactivation

Abstract BACKGROUND The Cytomegalovirus (CMV) is a ubiquitous herpes virus which infects 60–80 % of the population in Europe. Although the CMV usually remains latent, reactivation can occur in the context of an immunodepression, such as low CD4-lymphocyte levels in HIV patients. Glioblastoma (GBM) patients frequently show lymphopenia, which is related to both the immunosuppressive nature of the tumor and to the treatment with concomitant temozolomide (TMZ) and radiotherapy (RT). Surprisingly, the incidence of CMV reactivation in GBM patients has not been clearly studied so far. We report here our experience on CMV reactivation in a cohort of newly-diagnosed GBM patients, treated with RT and TMZ. We assessed the incidence of CMV reactivation in these patients and tried to identify risk factors for such reactivation. MATERIAL AND METHODS All consecutive patients with histologically confirmed malignant GBM recommended for temozolomide chemoradiotherapy in our institution from October 2013 to December 2015 were reviewed. In all patients, sex, age, Karnofsky performance status (KPS), lymphocyte level, serological CMV status and steroid dosages were recorded at the onset, and one month after completion of the concomitant radio-chemotherapy regimen. A CMV reactivation was defined by a detection of CMV DNA > 1000 copies/ml in the patient’s serum. RESULTS 103 patients meeting the analysis criteria were reviewed. Within these 103 patients, 34 patients (33%) had initial negative serology for CMV, and none of them developed a seroconversion after treatment with concomitant RT + TMZ. Among patients with positive IgG (n=69), 16 patients (23%) developed a positive viremia at one point during treatment with concomitant RT + TMZ. Age (>60 years), lymphocyte count before RT (<1500/mm3) and use of steroids were correlated with CMV reactivation (p<0.05 in univariate analysis). A positive CMV viremia during RT+TMZ did not impact the progression free survival (PFS) but was associated with a shorter overall survival (OS) when compared to the others patients (median: 12 months vs 15 months; p=0.04). No clinical symptoms suggestive of CMV infection were reported. CONCLUSION In this single center series, we showed that CMV reactivation occurs in 23% of the GBM patients having a positive serology for CMV. Reactivation was more frequent in older patients, with low lymphocyte counts and treated with steroids. A positive viremia was not associated with poor PFS, a fact that does not support a promoting role of CMV in glioma oncogenesis, which has been sometimes suggested. Yet, the group of patients with CMV reactivation showed a shorter OS, which might be related to an older age and /or poorer clinical conditions in this group.

Phase II study of FOLFOX, bevacizumab and erlotinib as initial therapy for patients with metastatic colorectal cancer (MCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3545-3545
Author(s):  
J. A. Meyerhardt ◽  
K. Stuart ◽  
A. Zhu ◽  
C. Fuchs ◽  
P. Bhargava ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Tolerability Profile ◽  
Egfr Inhibition ◽  
Grade 3

3545 Background: Cytotoxic chemotherapy with targeted therapy against the vascular endothelial growth factor (VEGF) or the epidermal growth factor receptor (EGFR) has become a standard approach in MCRC, though combining VEGF and EGFR inhibition with chemotherapy as initial treatment is not well established. We conducted a phase II study of the combination of infusional 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX), bevacizumab, and erlotinib in chemotherapy naïve patients with MCRC. Methods: Eligible patients had measurable MCRC, no prior systemic therapy for MCRC or at least one year since completion of adjuvant therapy (only 5-FU and leucovorin acceptable), performance status 0–1. The regimen consisted of 14-day cycles of FOLFOX started on day 1 (oxaliplatin 85 mg/m2, bolus 5-FU 400 mg/m2, leucovorin 400 mg/m2 and 46-hour infusion 5-FU 2.4 g/m2), day 1 bevacizumab 5 mg/kg and erlotinib 150 mg daily. This isa single stage trial with goal of 35 patients. The primary endpoint was progression-free survival (PFS). Results: Between Jan and Dec 2005, 31 patients have been enrolled with the following characteristics: male/female, 19/12; PS ECOG 0/1, 15/16; median age 58, range 38–81. Of the 28 patients who completed at least 1 cycle, the most common grade 3/4 adverse events include: 8/28 (29%) diarrhea, 8/28 (29%) neutropenia, 5/28 (18%) rash, 4/28 (14%) fatigue, 3/28 (11%) nausea/vomiting, 3/28 (11%) neuropathy. 22/28 (78%) of patients had at least 1 grade 3/4 toxicity. 14/31 patients remain on trial, 13/31 (42%) came off for toxicity or withdrew consent due to treatment-related toxicities, 4 withdrew consent for other reasons. Efficacy data is not available at time of submission but will be more mature by June 2006. Conclusions: The combination of FOLFOX, bevacizumab and erlotinib appears to have moderate toxicity, with ∼40% of patients coming off trial due to side effects. Further characterization of the tolerability profile will be necessary when interpreting the efficacy of the combination. We expect full accrual as well as reasonable point estimates of PFS by June 2006. Supported by: Sanofi-Synthelabo, a member of the Sanofi-Aventis group, Genentech [Table: see text]

Final results of a phase II study of erlotinib, docetaxel and cisplatin in patients with recurrent/metastatic head and neck cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6013-6013 ◽  
Author(s):  
E. S. Kim ◽  
M. S. Kies ◽  
B. S. Glisson ◽  
A. Tsao ◽  
L. E. Ginsberg ◽  
...  
Keyword(s):  
Growth Factor ◽  
Head And Neck ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Treatment Options ◽  
Single Agent ◽  
Progression Free Survival ◽  
Egfr Signaling Pathway ◽  
Grade 3

6013 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for recurrent/metastatic HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate as single agent in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75 mg/m2 and cisplatin 75 mg/m2 intravenously every 3 weeks and erlotinib 150 mg by mouth daily. All agents were started on day 1. Pts were treated with growth factor support. Results: The trial has completed accrual to 50 pts. 47 pts are available for analysis at this time. Median age is 56 years (range 39–72). ECOG PS is 0, 1, 2 (6, 29, 2 pts). 43 pts are evaluable for efficacy. All responses were confirmed via RECIST. Complete responses have been in observed in 4 pts, partial responses in 25 pts and 12 pts have stable disease for an overall response rate of 67% and disease control rate of 95%. After a follow-up of 19 months, median overall survival was 11 months (8.61, 22.5, 95% CI) and progression free survival was 6.01 months (4.37, 8.25). 6 pts had grade 3/4 febrile neutropenia, 4 pts had grade 3/4 dehydration, 3 pts had grade 3 diarrhea, and 2 pts had grade 3/4 GI bleeding. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusions: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in recurrent/metastatic HNSCC. Tissues are being collected and analyzed for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). Final efficacy and biomarker results will be presented at the annual meeting. No significant financial relationships to disclose.

SWOG S1216: A phase III randomized trial comparing androgen deprivation therapy (ADT) plus TAK-700 with ADT plus bicalutamide in patients (pts) with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) (NCT01809691).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5001-5001
Author(s):  
Neeraj Agarwal ◽  
Catherine Tangen ◽  
Maha H. A. Hussain ◽  
Shilpa Gupta ◽  
Melissa Plets ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Performance Status ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Meaningful Improvement ◽  
Intention To Treat ◽  
Grade 3

5001 Background: Tak is an oral selective nonsteroidal 17, 20-lyase inhibitor that blocks the synthesis of gonadal and adrenal androgens. We evaluated the clinical benefit of Tak with ADT in pts with newly diagnosed mHSPC. Methods: Pts with mHSPC with a Zubrod performance status (PS) of 0-2 and a PSA of ≥ 2 ng/ml were randomized 1:1 to ADT+Tak (300 mg twice daily) or ADT+Bic (50 mg daily). Stratification factors included PS (0-1 vs ≥2), extent of disease (minimal vs extensive), and receipt of ADT prior to registration (yes vs no). The primary endpoint was overall survival (OS). Secondary endpoints were progression free survival (PFS; based on PSA, imaging or clinical progression), PSA at 7 months (≤0.2 vs 0.2 < PSA; ≤-4 vs. > 4 ng/ml) and adverse event (AE) profile. With 2.75 yrs to accrue 1,186 eligible pts and 3 additional yrs of follow-up, we would have 90% power to determine a 33% improvement in OS from 54 to 72 mos (1-sided α = 0.025). A final analysis was pre-specified after 523 deaths using a 1-sided α = 0.022 to account for interim analyses. Results: Between 3/2013 and 7/2017, 1,313 pts were randomized and 1,279 were included in the intention-to-treat (ITT) analysis (32 pts were ineligible and 2 pts withdrew consent). Median age was 68 yrs and 10% of subjects were Black. Median PSA was 30 ng/mL (range 2-6710) and 49% of pts had extensive disease. After a median follow-up of 4.9 yrs, PFS and PSA response were significantly improved with Tak over Bic but no significant improvement in OS was observed (Table). More grade 3/4 AEs occurred in Tak vs. Bic arms (43% vs. 14%), and included hypertension (20% vs. 5%) and fatigue (5% vs. 2%). Five pts in Tak and 1 pt in the Bic arm had grade 5 AE. Conclusions: Despite clinically meaningful improvement in various outcome measures with Tak+ADT over Bic+ADT in this representative population of mHSPC, the improvement in OS did not meet the pre-specified criteria for statistical significance. The median OS of 70 mos in the control arm (standard ADT) was higher than that reported in contemporary phase 3 trials in this setting, and 16 mos higher than originally estimated. This trial sets a new landmark for survival estimates when pts with mHSPC have access to multiple approved subsequent life-prolonging therapies. Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819, U10CA180820; U10CA180821; and in part by Millennium Pharmaceuticals, Inc. (Takeda Pharmaceutical Company LTD) Clinical trial information: NCT01809691. [Table: see text]

scholarly journals A randomized phase II trial of efficacy and safety of the immunotherapy ALECSAT as an adjunct to radiotherapy and temozolomide for newly diagnosed glioblastoma

2021 ◽  
Author(s):  
Katja Werlenius ◽  
Giuseppe Stragliotto ◽  
Michael Strandeus ◽  
Malin Blomstrand ◽  
Helena Carén ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Open Label ◽  
Serious Adverse Events ◽  
Significant Difference

Abstract Background There is an urgent need for effective treatments against glioblastoma (GBM). In this trial we investigated the efficacy and safety of an adoptive cell-based immunotherapy. Methods Patients with newly diagnosed GBM were recruited at four study sites in Sweden. The patients were randomized 1:2 to receive either radiotherapy (RT), 60 Gy/30 fractions, with concomitant and adjuvant temozolomide (TMZ) only, or RT and TMZ with addition of Autologous Lymphoid Effector Cells Specific Against Tumor (ALECSAT) in an open-label phase II trial. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were survival and safety of ALECSAT. Results Sixty-two patients were randomized to either RT and TMZ alone (n=22) or RT and TMZ with ALECSAT (n=40). Median age was 57 years (range 38-69), 95% of the patients were in good performance status (WHO 0-1). There was no significant difference between the study arms (SOC vs. ALECSAT + SOC) in PFS (7.9 vs. 7.8 months; HR 1.28; 95% CI 0.70, 2.36; P=0.42), or in median overall survival (OS) (18.3 vs. 19.2 months; HR 1.16, 95% CI 0.58, 2.31; P=0.67). The treatment groups were balanced in terms of serious adverse events (52.4% vs. 52.5%), but adverse events ≥ grade 3 were more common in the experimental arm (81.0% vs. 92.5%). Conclusion Addition of ALECSAT immunotherapy to standard treatment with radiochemotherapy was well tolerated but did not improve PFS or OS for patients with newly diagnosed GBM.

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