Displaying One Session

Toledo Auditorium (Hall 5) Poster Discussion session
Date
28.09.2019
Time
08:45 - 09:45
Location
Toledo Auditorium (Hall 5)
Chairs
  • Dieta Brandsma (Amsterdam, Netherlands)
  • Olivier Chinot (Marseille, CEDEX 5, France)
  • Patrick Roth (Zürich, Switzerland)
Poster Discussion – CNS tumours Poster Discussion session

395PD - Circulating PD-L1 levels vary across brain tumour entities and are oppositely linked to survival in glioblastoma and lower grade glioma patients (ID 2990)

Presentation Number
395PD
Lecture Time
08:45 - 08:45
Speakers
  • Maximilian Mair (Vienna, Austria)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45

Abstract

Background

Immune therapies targeting the programmed cell death receptor (ligand) 1 (PD-1/PD-L1) axis have shown remarkable activity in a variety of solid tumors. While substantial responses were observed in asymptomatic patients with brain metastases (BM), their clinical activity in primary brain tumors remains limited. In a cohort of adult brain tumor patients, we aimed to analyze soluble PD-L1 (sPD-L1) levels in patient plasma as a systemic marker of tumor - immune system interactions.

Methods

We obtained EDTA plasma from 55 glioblastoma, 26 lower-grade (WHO grade II - III) glioma (LGG), 17 meningioma and 43 BM patients (29/43 lung cancer, 6/43 renal cell carcinoma, 4/43 breast cancer, 4/43 melanoma) as well as 25 controls. sPD-L1 concentrations were measured by a sandwich ELISA using an anti-PD-L1/CD274 antibody (Millipore ABF133) as capture antibody and a non-commercial anti-PD-L1 antibody (clone 5H1) as detection antibody. The lower detection limit as determined by serial dilutions of recombinant human PD-L1 was 0.050 ng/ml.

Results

sPD-L1 was identified in 41/81 (50.6%) glioma, 5/17 (29.4%) meningioma and 6/43 (14.0%) BM patient samples and in 9/25 (36.0%) controls (p = 0.001, Chi-square), with a median concentration of 0.415 ng/ml (range: 0.050 – 42.150 ng/ml). sPD-L1 concentrations were significantly lower in BM as compared to glioma patients (p < 0.001, Mann-Whitney-U) or controls (p = 0.028). There was no observable difference in sPD-L1 concentrations and detectability over WHO grades in glioma and meningioma patients. In BM patients, a trend towards different sPD-L1 levels between primary tumors was seen (p = 0.122, Kruskal-Wallis). sPD-L1 was not correlated to prognosis in meningioma and BM patients. In contrast, glioblastoma patients had longer overall survival (OS) when sPD-L1 was detected (p = 0.006, log-rank). Conversely, sPD-L1 detectability was linked to worse OS in LGG (p = 0.028).

Conclusions

Circulating PD-L1 levels differ between patients with distinct CNS malignancies, suggesting diverse tumor - immune system interactions between primary and secondary brain tumors. Moreover, our results indicate a differential prognostic impact of sPD-L1 in glioma which should be further studied.

Legal entity responsible for the study

The authors.

Funding

Medical University of Vienna.

Disclosure

A. Ilhan-Mutlu: Advisory / Consultancy: MSD; Advisory / Consultancy: Servier. M. Preusser: Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Gerson Lehrman Group (GLG); Honoraria (self), Advisory / Consultancy: CMC Contrast; Honoraria (self), Advisory / Consultancy: Mundipharma; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Medahead; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. A.S. Berghoff: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AbbVie. All other authors have declared no conflicts of interest.

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Poster Discussion – CNS tumours Poster Discussion session

396PD - Characterization of a novel BBB-permeable mutant IDH1 inhibitor, DS-1001b (ID 1774)

Presentation Number
396PD
Lecture Time
08:45 - 08:45
Speakers
  • Hironori Matsunaga (Tokyo, Japan)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45

Abstract

Background

Mutations in isocitrate dehydrogenase (IDH) 1 and 2 are frequently observed in glioma, acute myeloid leukemia (AML) and many other cancers. While wild-type IDHs convert isocitrate to α-ketoglutarate (α-KG), mutant IDHs convert α-KG to onco-metabolite 2-hydroxyglutarate (2-HG). Inhibitors of mutated IDH1 or IDH2 showed clinical benefits and were approved for AML patients, supporting IDH1/2 mutations are bona fide oncogenes. However, it remains unanswered whether inhibition of IDH1 mutant activity in glioma shows clinical benefits.

Methods

Small-molecule inhibitors for mutant IDH1 were synthesized and tested by in vitro IDH1 mutant enzymes and cell-based assays. DS-1001b is a tert-butylamine salt of DS-1001a. X-ray crystallography was applied to get the insight of inhibition mechanism. We used 14C-labelled DS-1001a to check the brain exposure of the compound. We used a glioblastoma patient-derived xenograft (PDX) model with heterozygous IDH1R132H to monitor the anti-tumor activity of DS-1001b.

Results

DS-1001b inhibited the enzymatic activities of IDH1R132H, IDH1R132C, and wild type IDH1 with IC50 values of 8, 11 and 180 nM, respectively, while it did not inhibit IDH2R140Q, IDH2R172Q, or wild type IDH2 (IC50 values of > 10000 nM). Through the analysis of X-ray crystallography of the ternary complex of IDH1R132C, NADPH, and compound A, a DS-1001b derivative, compound A was found in the allosteric pocket located at the dimer surface and IDH1R132C was in "open" inactive form. DS-1001b treatment inhibited production of 2-HG from cells with IDH1R132H or IDH1R132C at 20 – 50 nM. Brain exposure of the compound was tested in mice with radioactivity of [14C]DS-1001a, and the results suggested DS-1001a penetrates blood-brain barrier (BBB). Administration of DS-1001b showed great reduction of 2-HG in the tumor and clear anti-tumor effects against subcutaneous A1074 PDX model with heterozygous IDH1R132H.

Conclusions

Our results indicate that DS-1001b, which is currently in a phase I clinical trial for treating glioma with IDH1 mutations (NCT03030066), is BBB-permeable and effective against the PDX model of IDH1 mutant glioma through inhibition of IDH1 mutant proteins.

Clinical trial identification

NCT03030066.

Legal entity responsible for the study

Daiichi Sankyo Co., Ltd.

Funding

Daiichi Sankyo Co., Ltd.

Disclosure

H. Matsunaga: Full / Part-time employment: Daiichi Sankyo Co., Ltd. Y. Machida: Research grant / Funding (institution): Daiichi Sankyo Co., Ltd. M. Nakagawa: Research grant / Funding (institution): Daiichi Sankyo Co., Ltd. M. Yamaguchi: Research grant / Funding (institution): Daiichi Sankyo Co., Ltd. Y. Ogawara: Research grant / Funding (institution): Daiichi Sankyo Co., Ltd. Y. Shima: Research grant / Funding (institution): Daiichi Sankyo Co., Ltd. K. Yamagata: Research grant / Funding (institution): Daiichi Sankyo Co., Ltd. T. Katsumoto: Research grant / Funding (institution): Daiichi Sankyo Co., Ltd. A. Hattori: Research grant / Funding (institution): Daiichi Sankyo Co., Ltd. M. Itoh: Full / Part-time employment: Daiichi Sankyo Co., Ltd. T. Seki: Full / Part-time employment: Daiichi Sankyo Co., Ltd. Y. Nishiya: Full / Part-time employment: Daiichi Sankyo Co., Ltd. K. Nakamura: Full / Part-time employment: Daiichi Sankyo Co., Ltd. K. Suzuki: Full / Part-time employment: Daiichi Sankyo Co., Ltd. T. Imaoka: Full / Part-time employment: Daiichi Sankyo Co., Ltd. M. Suzuki: Full / Part-time employment: Daiichi Sankyo RD Novare Co., Ltd. K. Ichimura: Research grant / Funding (institution): Daiichi Sankyo. I. Kitabayashi: Research grant / Funding (institution): Daiichi Sankyo Co., Ltd. All other authors have declared no conflicts of interest.

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Poster Discussion – CNS tumours Poster Discussion session

397PD - Precision medicine for patients with primary brain tumours: Molecular screening for cancer treatment optimization (MOSCATO) prospective trial (ID 3522)

Presentation Number
397PD
Lecture Time
08:45 - 08:45
Speakers
  • Wafa Boulfoul (Villejuif, France)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45

Abstract

Background

Primary brain tumors are highly heterogeneous and current therapy confers only modest clinical benefit. There is a tremendous need for new therapeutic options and genomic profiling could help defining new strategies.

Methods

Data from patients with advanced primary brain tumors enrolled in the prospective clinical trial MOSCATO at the Drug Development Department (DITEP) at Gustave Roussy Cancer Center were retrospectively reviewed. Multiple high throughput molecular techniques were used to identify genetic mutations: Next Generation Sequencing (NGS), comparative genomic hybridization array (CGHa) and Foundation one CDx (FMI). Matched therapy was decided accordingly for patients who had targeted molecular alterations.

Results

Between April 2016 and December 2018, 103 patients with primary brain tumors were enrolled. Median age was 48 years (range, 19-75), median number of previous systemic therapies was 2 (range, 0–5), 98% had an ECOG performance status 0 or 1. The most prevalent histology was glioblastoma (70 %). Ten patients were screen failure due to unavailability of tumor tissue and no possibility of new brain biopsy. Eighty-nine molecular analyses were successful (CGH: N = 45, NGS: N = 47, FMI: N = 42). Median time between consent and results was 49 days (range, 18-235). Tumor mutational burden (TMB) was available in 42 pts and was considered low (<6) in 33 patients. Altogether, 365 actionable alterations were detected: amplification (n = 82; 22.5 %), deletion (n = 76; 21%), mutation (n = 197; 54 %) and rearrangement (n = 10 ; 2.7 %). Most frequent alterations were: CDKN2A/2B (10%), EGFR (9.1%), TP53 (8.6%), TERT p (7.4%), PTEN (6.8%). Thirty patients (34%) were oriented to a matched therapy according to actionable alterations, five of them being treated with targeted therapies (BRAF inhibitor; n = 1, EGFR inhibitor; n = 1, mTOR inhibitor; n = 1, FGFR inhibitor; n = 1, TKI-VEGFR n = 1).

Conclusions

Molecular profiling in patients with primary brain tumors is feasible and can lead to orientation in clinical trials and/or treatment with targeted therapies. However the reasons for the small number of patients finally treated are currently under investigations and will be presented at the conference.

Legal entity responsible for the study

Christophe Massard.

Funding

Institut Gustave Roussy.

Disclosure

C. Baldini: Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Abbvie; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Amgen; Speaker Bureau / Expert testimony: Sanofi. L. Verlingue: Speaker Bureau / Expert testimony: Adaptherapy; Speaker Bureau / Expert testimony: Pierre Fabre; Research grant / Funding (self): BMS. E. Angevin: Advisory / Consultancy: Merck; Advisory / Consultancy: GSK; Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: Abbvie; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Pfizer. A. Varga: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Astra Zeeneca; Speaker Bureau / Expert testimony: MSD. S. Postel Vinay: Research grant / Funding (self): Merck; Research grant / Funding (self): Boehringer; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: AstraZeneca; Travel / Accommodation / Expenses: AstraZeneca. A. Gazzah: Travel / Accommodation / Expenses: Boehringer; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Novartis. R. Bahleda: Travel / Accommodation / Expenses: Taiho; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Boehringer. A. Marabelle: Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Onxeo; Advisory / Consultancy: EISAI; Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Genticel; Advisory / Consultancy: Rigontec; Advisory / Consultancy: Diachii; Advisory / Consultancy: Imaxio; Advisory / Consultancy: Sanofi; Advisory / Consultancy: BioNtech; Advisory / Consultancy: Corvus; Advisory / Consultancy: Deerfield; Advisory / Consultancy: Bioncotech; Research grant / Funding (self): Merus; Research grant / Funding (self): BMS; Research grant / Funding (self): Boehringer; Research grant / Funding (self): Transgene. V. Ribrag: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Nanostring Technologies; Speaker Bureau / Expert testimony: Servier; Honoraria (self): Eisai. S. Champiat: Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Janssen. J. Michot: Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Janssen. A. Hollebecque: Advisory / Consultancy: Amgen; Advisory / Consultancy: Spectrum Pharmaceuticals; Advisory / Consultancy: Lilly; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Lilly; Speaker Bureau / Expert testimony: Bayer. J. Soria: Full / Part-time employment: Medimmune. C. Massard: Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Beigene; Advisory / Consultancy: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: Debiopharm; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Lilly; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Medimmune; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi. All other authors have declared no conflicts of interest.

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Poster Discussion – CNS tumours Poster Discussion session

Invited Discussant 395PD, 396PD and 397PD (ID 6688)

Lecture Time
08:45 - 09:00
Speakers
  • Olivier Chinot (Marseille, CEDEX 5, France)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45
Poster Discussion – CNS tumours Poster Discussion session

Q&A led by Discussant (ID 6692)

Lecture Time
09:00 - 09:05
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45
Poster Discussion – CNS tumours Poster Discussion session

398PD - Extending temozolomide longer than six cycles in glioblastoma: Results of the randomized GEINO-014 trial (ID 4589)

Presentation Number
398PD
Lecture Time
09:05 - 09:05
Speakers
  • Maria Angeles V. Vaz Salgado (Madrid, Spain)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45

Abstract

Background

Standard treatment of glioblastoma (GBM) is focal radiation with concomitant and adjuvant temozolomide (TMZ) for 6 cycles. The GEINO-14-01 trial (NCT02209948) investigated the role of extending adjuvant TMZ to 12 cycles in a randomized multicenter study.

Methods

Between Aug/2014 and Nov/2018, 166 patients (p) were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment to 12 cycles after proving lack of progression of the disease in the MRI performed before inclusion. The trial was stratified by MGMT status and presence or absence of residual disease (defined as a residual enhancement larger than 1cm on the MRI). The primary endpoint was differences in 6monthsPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors.

Results

Median age was 60.4 (range 29-83), all p had ECOG≤1 and 86.2% were without DXM treatment. MGMT status: Met: 97 (61%) UnMet:62 (39%). RD yes: 83 (52.2%) and no: 76 (47.8%). At the time of the abstract report 3 patients are still on treatment or control without a documented progression and 5 patients have not been yet 6m in the study: 31 patients (19.5) are still free of progression and 60 patients (37.7%) are still alive. Median (m) PFS has been reached: 7.9 months (95%CI: 6.1-9.8) as well as mOS: 20.9 (95%CI: 17.6-24.1). A methylated status was a factor of better PFS (HR = 0.29, 95% CI 0.46-0.95; p = 0.029) and better OS (HR = 0.43: 95% CI 0.28-0.66; p = 0.000) as well as the absence of residual disease (PFS: HR = 0.84: 95% CI = 0.71-1.01; p = 0.068; OS: HR = 0.77, 95%CI 0.63-0.96; p = 0.019). We didn’t find any difference in PFS (HR = 1.02, 95%CI 0.85-1.21; p = 0.82), or OS (HR = 0.90; 0.73-1.11; p = 0.34) on extending treatment with temozolomide longer than 6 cycles. Toxicity data and final results are expected for the congress.

Conclusions

There is no benefit of continuing TMZ treatment for more than 6 cycles in the adjuvant treatment of glioblastoma. Met status and absence of RD are factors of better SLP after adjuvant treatment. Supported by a Grant of the ISCIII: PI13/01751.

Clinical trial identification

NCT02209948.

Legal entity responsible for the study

GEINO (Grupo Español de Investigación en Neurooncologia).

Funding

Supported by a Grant of the ISCIII.

Disclosure

M.A.V. Salgado: Advisory / Consultancy: Lilly; Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: pharmamar; Advisory / Consultancy: eisai; Advisory / Consultancy: Celgene. All other authors have declared no conflicts of interest.

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Poster Discussion – CNS tumours Poster Discussion session

399PD - Association of systemic inflammation with local tumour characteristics and survival in glioma patients (ID 3553)

Presentation Number
399PD
Lecture Time
09:05 - 09:05
Speakers
  • Pegah Mir Seyed Nazari (Vienna, Austria)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45

Abstract

Background

Immunotherapy has yield only modest clinical efficacy in glioma so far. However, gliomas are characterized by a range of immune suppressive features. Here, we aimed to analyze the correlation of systemic inflammation with local tumor characteristics and overall survival in glioma patients.

Methods

Glioma patients were recruited at time of diagnosis or recurrence within the Vienna Cancer and Thrombosis Study (CATS). At study inclusion, a blood draw was performed. IDH1 mutation, PD-L1 and podoplanin in glioma were assessed via immunohistochemistry.

Results

193 glioma patients (4.7% diffuse glioma, 19.7% anaplastic glioma, 75.6% glioblastoma) were included. IDH1 mutation was present in 40/193 (20.7%) patients, PD-L1 expression was observed in 20/193 (10.4%) patients, and podoplanin positivity was found in 134/193 (69.4%) patients. IDH1 mutation was associated with higher platelet count (median: 303 vs. 232 G/L, p = 0.001) and lower neutrophil count (4.71 vs 6.55 G/L, p = 0.021) as well as lower neutrophil/lymphocyte (N/L) ratio (3.34 vs. 5.13, p = 0.016). PD-L1 was associated with higher monocyte count (0.657 vs. 0.450 G/L, p = 0.008), higher C-reactive protein (CRP) (0.43 vs. 0.1 mg/dL, p = 0.005) and higher fibrinogen (379 vs. 303 mg/dL, p = 0.001). Podoplanin was associated with higher leukocyte count (8.88 vs 7.22 G/L, p = 0.040), higher neutrophil count (6.44 vs 5.03 G/L, p = 0.048), higher N/L ratio (5.4 vs. 3.2, p = 0.006) and lower platelet count (227 vs 289 G/L, p < 0.0001). Upon multivariable adjustment for sex and age, platelet count (hazard ratio per 1 unit increase: 0.997, 95% CI [0.995-0.999], p = 0.006), leukocyte count (1.040 [1.004-1.077], p = 0.030), neutrophil count (1.043 [1.000-1-087], p = 0.049) and CRP levels (1.095 [1.010-1-187], p = 0.027) correlated with overall survival.

Conclusions

Systemic inflammation correlated with overall survival in the present glioma cohort. Furthermore, molecular glioma characteristics (IDH1 mutation, PD-L1, podoplanin) were linked to distinct systemic inflammation patterns. Clinical trials on immune modulating therapies should consider these different glioma-immune system interactions in order to potentially select patients with the highest benefit.

Legal entity responsible for the study

Medial University of Vienna.

Funding

Austrian National Bank.

Disclosure

P. Mir Seyed Nazari: Travel / Accommodation / Expenses: Bayer. M. Preusser: Research grant / Funding (self): Böhringer-Ingelheim; Research grant / Funding (self): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dome; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Gerson Lehrman Group (GLG); Honoraria (self), Advisory / Consultancy: CMC Contrast; Honoraria (self), Advisory / Consultancy: GlaxoSmithKline,; Honoraria (self), Advisory / Consultancy: Mundipharma; Honoraria (self), Advisory / Consultancy: Astra; Honoraria (self), Advisory / Consultancy: Zeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Medahead; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. A.S. Berghoff: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Meyers Squibb; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AbbVie. All other authors have declared no conflicts of interest.

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Poster Discussion – CNS tumours Poster Discussion session

400PD - Characteristics and patterns of care of high-grade IDH-mutant gliomas in elderly patients: A French POLA network study (ID 1587)

Presentation Number
400PD
Lecture Time
09:05 - 09:05
Speakers
  • Coline Montegut (Marseille, France)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45

Abstract

Background

The characteristics of elderly patients with IDH-mutant (IDHm) high-grade gliomas (HGG) remain to be described. This study aims to describe characteristics and patterns of care of elderly patients with IDHm HGG included in the French POLA network dedicated to HGG.

Methods

The characteristics and patterns of care of elderly (≥70 years) patients IDHm HGG were compared to those of younger patients (<70 years) with IDHm gliomas and to those of elderly patients with IDH wild-type (IDHwt) gliomas.

Results

Out of the 1433 HGG patients included, 119 (8.3%) occurred in elderly patients. Histology consisted of 1p/19q codeleted anaplastic oligodendroglioma (71.8%), anaplastic IDHm astrocytomas (12.8%) and IDHm glioblastoma (15.4%). Median age at diagnosis was 74 years (70.2-87.1), median Karnofsky Performans Status (KPS) was 80 (50-100). Treatments consisted of a wait and scan policy (7.7%), radiotherapy (RT) alone (7.7%), chemotherapy (CT) alone (41%), RT-CT (RT-TMZ: 25.6%, RT-PCV: 15.4%) or palliative care (2.6%). The clinical, radiological and histological presentations of elderly patients IDHm HGG were different from those of elderly patients IDHwt HGG. Compared to elderly patients IDHwt HGG, elderly patients IDHm were less frequently associated with cognitive impairment (p = 0.045), contrast enhancement (p = 0.01) and had a lower proliferative index (Ki67) (p = 0.005). In contrast, there was no difference regarding clinical, radiological and histological presentations of elderly and younger patients IDHm HGG but their management was different. Elderly patients IDHm less frequently underwent gross total resection (p = 0.002) and radiotherapy (p < 0.001). The median progression-free survival (PFS) and overall survival (OS) were longer for IDHm elderly patients (29.2 and 62.1 months respectively) than IDHwt elderly patients (8.2 and 13.2 months respectively) but shorter than younger IDHm patients (69 months and not reached respectively).

Conclusions

IDHm HGG in elderly show prolonged survival. However, their poorer outcome compared to younger IDHm gliomas may results from patient or tumor characteristics or from under-treatment, suggesting a role for geriatric assessment.

Legal entity responsible for the study

French POLA network.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion – CNS tumours Poster Discussion session

401PD - GEINO 1402: A phase Ib dose-escalation study followed by an extension phase to evaluate safety and efficacy of crizotinib in combination with temozolomide (TMZ) and radiotherapy (RT) in patients with newly diagnosed glioblastoma (GB) (ID 3418)

Presentation Number
401PD
Lecture Time
09:05 - 09:05
Speakers
  • Maria Martinez Garcia (Barcelona, Spain)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45

Abstract

Background

MET signaling has a role in gliomagenesis and glioma stem cell maintenance and midkine (ALK ligand) promotes resistance of glioma cells to anticancer therapies. Crizotinib is an ALK and c-MET inhibitor with a preclinical rationale to be tested in newly diagnosed GB.

Methods

Elegible patients received crizotinib in addition to standard RT and TMZ and then adjuvant TMZ. Maintenance treatment with crizotinib beyond 6 TMZ cycles was allowed. The primary objective was safety evaluation. Secondary objectives included efficacy (progression free survival (PFS) and overall survival (OS)) and an exploratory biomarker analysis. PFS and OS were estimated with Kaplan–Meier method. The results of the dose-escalation cohort (DE) have been reported previously. 250 mg/d was the crizotinib dose selected for the expansion cohort (EC). We report here safety and efficacy for the whole cohort.

Results

38 patients (pts) were enrolled, 37 evaluable for safety and 36 for efficacy (12 included in DE). Median age 52 years (33-76). 44%were male. Median KPS 90%, Barthel 100%. 44% were MGMT methylated and 3 pts had IDH1/2 mutation. Most common related adverse events (AE) (all grades) included: nausea (67.6%), asthenia (62.2%), transaminase elevation (40.5%), neutropenia (32.4%) thrombocytopenia (29.7%), diarrhea (29.7%), anorexia (29.7%), vomiting (27%) and constipation (24.3%). In the EC 8/25 pts (32%) presented grade ≥3 AEs (transaminase elevation, thrombocytopenia). 97.2% finished concomitant therapy. 94.4% initiated adjuvant treatment, 67.7% completed 6 TMZ cycles. 18 pts (50%) started maintenance therapy. 8 pts are still on treatment. At the time of this analysis 24 pts have progressed and 1 died without progression. Median follow up was 13.7 months (m), median PFS was 10.78m (95% CI, 7.61-13.94), with 6 month PFS and 12 month PFS of 71.6% and 40.2% respectively. Median OS was 31.4 m(95% CI, 12.64-50.10) with 12month OS of 78.9% and 24month OS of 56.6%.

Conclusions

In this phase Ib study addition of crizotinib to standard RT and TMZ was safe and resulted in highly promising efficacy for newly diagnosed GB, deserving further investigation.

Clinical trial identification

NCT02270034.

Legal entity responsible for the study

GEINO.

Funding

PFIZER.

Disclosure

M. Martinez Garcia: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: ROCHE; Travel / Accommodation / Expenses: PFIZER. E. Pineda: Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Amgen. All other authors have declared no conflicts of interest.

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Poster Discussion – CNS tumours Poster Discussion session

Invited Discussant 398PD, 399PD, 400PD and 401PD (ID 6690)

Lecture Time
09:05 - 09:20
Speakers
  • Patrick Roth (Zürich, Switzerland)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45
Poster Discussion – CNS tumours Poster Discussion session

Q&A led by Discussant (ID 6693)

Lecture Time
09:20 - 09:25
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45
Poster Discussion – CNS tumours Poster Discussion session

402PD - Impact of neurological symptom burden on the survival prognosis in a real-life cohort of patients with non-small cell lung cancer brain metastases (ID 3331)

Presentation Number
402PD
Lecture Time
09:25 - 09:25
Speakers
  • Ariane Steindl (Vienna, Austria)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45

Abstract

Background

The high efficacy of targeted treatments in a- to oligosymptomatic non-small cell lung cancer (NSCLC) brain metastases (BM) revived the long discussion on BM screening. Therefore, we aimed to investigate the prognostic impact of symptomatic burden in patients with newly NSCLC BM in a large real-life cohort.

Methods

Patients with newly diagnosed NSCLC BM were identified from the Vienna Brain Metastasis Registry.

Results

1531 patients (male 57.4%, female 42.3%; median age 62 years) were available for further analysis. Neurological symptoms including neurological deficits (952/153; 62.2%), symptoms of increased intracranial pressure (456/153; 29.8%) and epileptic seizures (199/1531; 13.0%) were evident in 1125/1531 (73.5%) patients. Oligo-to asymptomatic BM were significantly more frequently observed in patients with synchronous diagnosis of BM and NSCLC (p < 0.001). Patients with oligo- to asymptomatic BM presented with a longer median overall survival after diagnosis of BM compared to patients with symptomatic BM (11 vs. 7 months; p < 0.001). In detail, presence of increased intracranial pressure and seizures showed no impact on survival prognosis (p > 0.05), while the median overall survival was significantly longer in patients without neurological deficits (11 vs. 7 months; p < 0.001): memory disorders (6 vs. 8 months; p > 0.05), ataxia (7 vs. 8; p = 0.041) and vertigo (6 vs. 9; p = 0.007). In multivariate analysis with DS-GPA (HR 1.41; 95% CI 1.33-1.50; p < 0.001), the presence of neurological symptoms was independently associated with survival prognosis from diagnosis of BM (HR 1.19; 95% CI 1.05-1.36; p = 0.007). Interestingly, the prognostic impact of neurological symptoms was more pronounced in patients with lower DS-GPA class II-IV (class II: 15 vs. 11; p = 0.002, class III: 10 vs. 6; p < 0.001, class IV: 6 vs. 3; p = 0.018) compared to patients with DS-GPA class I (19 vs. 14; p = 0.230).

Conclusions

Presence of neurological symptoms presented with a strong and independent association with survival prognosis from diagnosis of BM especially in patients with lower DS-GPA and should be further evaluated for inclusion in the prognostic assessment of patients with newly diagnosed NSCLC BM.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Preusser: Research grant / Funding (self): Böhringer-Ingelheim; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (self): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dome; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Gerson Lehrman Group; Honoraria (self), Advisory / Consultancy: CMC Contrast; Honoraria (self), Advisory / Consultancy: Mundipharma; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Medahead; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. A.S. Berghoff: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Meyers Squibb; Honoraria (self), Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AbbVie. All other authors have declared no conflicts of interest.

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Poster Discussion – CNS tumours Poster Discussion session

403PD - Tumour mutational burden and immune infiltrates in primary renal cell carcinoma and matched brain metastases (ID 3348)

Presentation Number
403PD
Lecture Time
09:25 - 09:25
Speakers
  • Ariane Steindl (Vienna, Austria)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45

Abstract

Background

High tumor mutational burden (TMB) as well as high density of tumor infiltrating lymphocytes (TIL) have been postulated as predictive response biomarkers for immune checkpoint inhibitor-based therapies. Therefore, we aimed to investigate the concordance of TMB and TIL in a series of primary/extracranial renal cell carcinoma specimens and matched brain metastases (BM).

Methods

Specimens from 10 patients with brain metastatic renal cell carcinoma were retrieved from the Vienna Brain Metastasis Registry (6/10 primary renal cell tumor, 4/10 lung metastasis, 10/10 matched BM). TMB was assessed using the TruSight Oncology 500 gene panel with libraries sequenced on a NextSeq instrument. TIL subsets (CD3+, CD8+) were investigated using the Ventana Benchmark Ultra system for immunohistochemistry and automated tissue analysis (Definiens software).Spearman correlation coefficient (SCC) and paired t-test were used to correlate and compare scale variables.

Results

Median TMB was 5.4 mut/Mb (range 0-8.6 mut/Mb) in extracranial samples and 5.9 mut/Mb (range 3.1 – 59.6 mut/Mb) in BM (p > 0.05; paired t-test). Median density of CD3+ TIL in extracranial samples was 3.7/nm2 (range 4.9 – 7.1/nm2) and 5.2/nm2 (range 7.0 – 9.8/nm2) in BM (p > 0.05; paired t-test). Median density of CD8+ TIL was 3.2/nm2 (range 4.4 – 8.7/nm2) in extracranial samples and 3.7/nm2 (range 5.9 – 8.8/nm2) in BM (p > 0.05; paired t-test). No significant correlation of CD3+ TIL density and TMB (SCC: 0.02), CD8+ TIL density and TMB (SCC: 0.42) nor CD3+ and CD8+ TIL density (SCC: 0.18; p > 0.05) was observed in the present cohort.

Conclusions

TMB and TIL density were numerically higher in BM compared to the matched extracranial samples in the present cohort. Although results have to be interpreted with caution due to the limited sample size, our results support the further exploration of immune checkpoint inhibitors also in patients with BM from renal cell carcinoma.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Preusser: Research grant / Funding (self): Böhringer-Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dome; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Gerson Lehrman Group; Honoraria (self), Advisory / Consultancy: CMC Contrast; Honoraria (self), Advisory / Consultancy: Mundipharma; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Medahead; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. A.S. Berghoff: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Meyers Squibb; Honoraria (self), Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AbbVie. All other authors have declared no conflicts of interest.

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Poster Discussion – CNS tumours Poster Discussion session

Invited Discussant 402PD and 403PD (ID 6691)

Lecture Time
09:25 - 09:40
Speakers
  • Dieta Brandsma (Amsterdam, Netherlands)
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45
Poster Discussion – CNS tumours Poster Discussion session

Q&A led by Discussant (ID 6694)

Lecture Time
09:40 - 09:45
Location
Toledo Auditorium (Hall 5), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:45 - 09:45