ESMO Supporter 2018

Displaying One Session

Hall B3 - Room 20 Proffered Paper session
Date
19.10.2018
Time
16:00 - 17:30
Location
Hall B3 - Room 20
Chairs
  • Carmen Balana (Badalona, ES)
  • Matthias Preusser (Vienna, AT)
Proffered Paper session - CNS tumours Proffered Paper session

371O - Intra-CSF liposomal cytarabine plus systemic therapy as initial treatment of breast cancer leptomeningeal metastasis: a randomised, open-label trial

Presentation Number
371O
Lecture Time
16:00 - 16:12
Speakers
  • Emilie Le Rhun (Lille, FR)
Location
Hall B3 - Room 20, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

The role of intra-cerebrospinal fluid (CSF) therapy for the treatment of leptomeningeal metastasis (LM) remains controversial.

Methods

We conducted a multicenter randomized open-label study to explore the effect of the addition of liposomal cytarabine to systemic therapy for the treatment of LM from breast cancer. Inclusion was based on the detection of tumor cells in the CSF or typical clinical and magnetic resonance imaging (MRI) signs of LM. Patients were randomly assigned to receive systemic therapy alone (arm A) or systemic therapy plus intra-CSF liposomal cytarabine (5 injections of 50 mg x 2 weeks, followed by monthly injections of 50 mg until progression, unacceptable toxicity or for 1 year) (arm B). Neurological and quality of life evaluation was performed monthly, cerebrospinal MRI every 2 months. The primary endpoint was progression-free survival in the leptomeningeal compartment (LM-PFS); 66 were required to ensure 80% power for a hazard ratio of 0.5, and a two-sided alpha=5%. Overall survival (OS) was a secondary efficacy endpoint.

Results

Thirty-seven patients were assigned to arm A, 36 patients to arm B. Baseline characteristics were similar in both arms. The median number of liposomal cytarabine injections in arm B was 5 (range 1-20). Focal radiotherapy was performed in 6 (16%) and 5 (14%) patients in arms A and B, respectively. Serious adverse events were reported in 6 and 14 patients in arms A and B. In the intent-to-treat population, median LM-PFS as assessed by the local investigator was 2.0 months (95% confidence interval (CI) 1.3 – 2.7) in arm A versus 4.3 months (95% CI 2.3 – 5.7) in arm B (HR = 0.57, 95% CI 0.35 – 0.92, p = 0.02). Sixty-eight patients have died. Actuarial median OS was 4.0 months (95% CI 2.2-6.5) in arm A versus 7.3 months (95%CI 3.9-12.6) in arm B (HR = 0.80, 95% CI 0.50-1.29, p = 0.35). Centrally reviewed LM-PFS, patient-reported outcomes (quality of life, functional, emotional status) over time will also be reported.

Conclusions

The addition of liposomal cytarabine to systemic therapy may improve LM-related PFS but does not significantly improve survival. Quality of life data will be essential to determine a possible clinical benefit afforded by intrathecal chemotherapy.

Clinical trial identification

NCT01645839.

Legal entity responsible for the study

Oscar Lambret Center, Lille, France.

Funding

Mundipharma.

Editorial Acknowledgement

None

Disclosure

E. Le Rhun: Research funding: Mundipharma; Honoraria for lecture: Mundipharma. M. Weller: Honoraria for lecture: Mundipharma. All other authors have declared no conflicts of interest.

Collapse
Proffered Paper session - CNS tumours Proffered Paper session

372O - Mutational and inflammatory microenvironment characteristics in primary and matched local recurrent non-small cell lung cancer brain metastases

Presentation Number
372O
Lecture Time
16:12 - 16:24
Speakers
  • Anna Sophie Berghoff (Vienna, AT)
Location
Hall B3 - Room 20, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

Tumor heterogeneity in mutational as well as inflammatory characteristics is a proposed major driver of treatment resistance and tumor progression. Given that the majority of patients with brain metastases (BM) develop brain relapse during their clinical course, we aimed to investigate the mutational and immunological heterogeneity in BM.

Methods

Patients treated with neurosurgical resection of a newly diagnosed BM from non-small cell lung cancer and subsequent neurosurgical resection of the local BM recurrence were identified from the Vienna Brain Metastasis Registry. Whole exome sequencing and analysis of tumor infiltrating lymphocytes (TILs) using immunohistochemistry was performed.

Results

24 matched BM specimens from 12 patients (9/12 (75%) male; median age 60 years) were available for analysis. A high concordance in CD3+ TIL (p = 0.004) and CD8+ TIL (p = 0.004) density as well as in the tumor mutational burden (TMB; p < 0.001) was evident between the two specimens of the same patient. A single case (1/12 (8.3%)) changed from low CD3+ and CD8+ TIL density to high density although no radiotherapy or immunotherapy was applied in-between. TMB in the first resection specimen (median 39.2 mutations / Mb) correlated with TMB in the second resection specimen (39.3 mutations / Mb; p < 0.001). A single case (1/12 (8.3%)) presented with marked TMB increase (154 mutation/Mb to 217 mutation/Mb) after application of stereotactic radiotherapy to the resection cavity. No correlation of TIL density and TMB was evident in the investigated specimens (p > 0.05). Overall the mutational characteristics were stable between the two specimens at the same location but at different time points of the same patients as 88% (range 80%-93%) of mutations were shared by both samples.

Conclusions

High concordance in mutational and immunological characteristics was observed in this homogenous cohort of local non-small cell lung cancer BM recurrences. TIL density as well as TMB were consistent between BM and the matching local recurrence, although radiotherapy might impact the mutational characteristics. Further analysis of the mutational differences might reveal new therapeutic approaches for secondary BM prevention.

Legal entity responsible for the study

Medical University of Vienna.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Proffered Paper session - CNS tumours Proffered Paper session

Invited Discussant 371O and 372O

Lecture Time
16:24 - 16:39
Speakers
  • Joan Seoane (Barcelona, ES)
Location
Hall B3 - Room 20, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30
Proffered Paper session - CNS tumours Proffered Paper session

373O - Results of Phase 2 Trial of SL-701, a novel immunotherapy targeting IL-13Ra2, EphA2, and survivin, in adults with second-line recurrent glioblastoma (GBM)

Presentation Number
373O
Lecture Time
16:39 - 16:51
Speakers
  • David Peereboom (Cleveland, US)
Location
Hall B3 - Room 20, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

SL-701 is a novel immunotherapy comprised of synthetic peptides designed to elicit an anti-tumor immune response against targets overexpressed in glioblastoma (GBM): interleukin-13 receptor alpha-2, ephrinA2 and survivin. Updated phase 2 data are reported.

Methods

Patients enrolled had recurrent GBM, were HLA-A2+ and bevacizumab (bev)-naïve, and had KPS>60. In Stage 1, SL-701 was administered with adjuvants GM-CSF and imiquimod biweekly for 6 months, then q28 days. In Stage 2, SL-701 and adjuvant poly-ICLC were administered biweekly with bev (10 mg/kg) for 6 months, then q28 days. Primary objectives included safety, tolerability, investigator-assessed objective response rate (ORR) using RANO criteria, and 12-month overall survival rate (OS-12). SL-701-specific CD8+ T cells in PBMCs isolated from patients were assessed by flow cytometry using antibodies to CD3, CD4, CD8, IFNg, TNFa, IL-2, and PD-1.

Results

Accrual for Stages 1 and 2 is complete. 74 patients [46 in Stage 1 and 28 in Stage 2; 65% male, median age of 57 years [(range: 24-79)] received SL-701. Five patients received SL-701 on compassionate use basis. The most frequent treatment-related adverse events (TRAEs) were fatigue (22%) and injection site reaction (18%). The most frequent grade 3-4 treatment-related adverse event was fatigue (n = 2; 2.7%). In Stage 1, a 22% disease control rate (DCR; CR+PR+SD for > =8 weeks) was observed, comprised of 1 PR (duration: 78 weeks) and 9 SD [median duration: 25 weeks (range: 3.7–120.9)] were observed. In Stage 2, a 54% DCR was observed consisting of 2 CRs (duration: 22 and 46 weeks), 2 PRs (duration: 38 and 54 weeks), and 11 SDs [median duration: 13.6 weeks (range: 1.6 – 35.1)] were observed. OS-12 was 44% in Stage 1 [95% CI 28.9, 58.9] and 50% [95% CI 30.6, 69.4] in Stage 2, and median OS was 11 months in Stage 1 and 11.7 months in Stage 2. Flow cytometry analysis of Stage 2 patients demonstrated CD8+ T cell responses to the SL-701 peptides.

Conclusions

SL-701 plus adjuvants with or without bevacizumab was well-tolerated and demonstrated anti-tumor activity, including multiple major responses and a preliminarily promising survival curve, warranting further study. Updated study data will be presented.

Clinical trial identification

NCT02078648.

Legal entity responsible for the study

Stemline Therapeutics.

Funding

Stemline Therapeutics.

Disclosure

R. Lindsay, J. Bullington, C. Brooks: Employment and stock ownership: Stemline Therapeutics. All other authors have declared no conflicts of interest.

Collapse
Proffered Paper session - CNS tumours Proffered Paper session

374O - Mismatch repair deficiency (MMRd) in glioma patients (PTS): frequency and correlation with clinical, histological and molecular characteristics

Presentation Number
374O
Lecture Time
16:51 - 17:03
Speakers
  • Giuseppe Lombardi (Padova, IT)
Location
Hall B3 - Room 20, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

Immune-checkpoint inhibitors (ICI) represent a new interesting approach in oncology. The presence of DNA MMRd would seem to be a predictor of ICI efficacy. We analyzed MMRd frequency in glioma PTS and its correlation with clinical, histological and molecular characteristics.

Methods

From July 2017 to May 2018, we prospectively analyzed histologically confirmed glioma PTS for the presence of MMRd by immunohistochemistry (IHC): MSH2, MSH6, PMS2, MLH1. Clinical, histological and molecular characteristics (MGMT methylation and IDH mutational status, PD-L1 expression) were recorded. Chi-square test was used for analyzing their correlations with MMRd.

Results

167 PTS were enrolled: 78% glioblastoma (GBM), 14% anaplastic astrocytoma (AA), 1% ependymoma, 2% anaplastic oligodendroglioma (OD) and 5% LGG. The analyses were assessed on tissue samples of first (82% of the cases) and second surgery (18%). All PTS performing a second surgery received radiotherapy and temozolomide as first-line therapy. 134 PTS were analyzed for IDH status: 99 were IDH wt; 117 for MGMT status: 68 were methylated. 27 PTS (16%) showed MMRd by IHC (MSH2 in 48%, MSH6 in 55.6%, PMS2 in 18.5% and MLH1 in 14.8%): 33% of AA, 14% of GBM, 33% of OD and 0% of LGG (p = 0.2). MMRd was found in 13% and 32% on first and second surgery samples (p = 0.03). PD-L1 expression analysis was performed in 60 cases: no expression was showed in 58% of cases, ≥ 1% and <50% in 38%, > 50% in 10%. MMRd was not correlated with PD-L1 expression (p = 0.3). MMRd was found in 10% and 29% of IDHwt and IDHmut gliomas (p = 0.008); MMRd was showed in 10% and 21% of PTS with unmet and metMGMT (p = 0.1). Among MMRd tumors, 7 were also investigated by molecular analysis (PCR) of mononucleotide markers: in only 1 PT (14%) was confirmed MMRd in agreement with IHC analysis (p = 0.1.).

Conclusions

We showed a small group of glioma PTS have MMRd by IHC, expecially at second surgery. Correlation was observed between IHC MMRd and IDH mutational status. No association was demonstrated between IHC MMRd and histology, MGMT status, PD-L1 expression or molecular analysis of MMRd. A prospective study analyzing ICI efficacy in MMRd PTS should be warranted.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Proffered Paper session - CNS tumours Proffered Paper session

375O - radiological phenotyping of idh mutation status in gliomas using dynamic susceptibility contrast perfusion-weighted mri.

Presentation Number
375O
Lecture Time
17:03 - 17:15
Speakers
  • Diana Roettger (London, GB)
Location
Hall B3 - Room 20, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

Gliomas staging and prognosis has been recently related to the mutation of the gene encoding isocitrate dehydrogenase (IDH). Dynamic Susceptibility Contrast Perfusion-Weighted Imaging (DSC-PWI) is an established MRI technique for glioma staging and prognosis but its value for non-invasive IDH phenotyping has not been thoroughly investigated. Combining DSC-PWI with advanced image analysis methods, such as texture analysis and machine learning, has the potential to increase the diagnostic accuracy of DSC MRI for IDH mutation status detection.

Methods

Our retrospective, multi-centre study included 365 patients [184 female; 181 male, median age: 49 (range 21-81 years)], who had been immunohistopathologically diagnosed with gliomas (198 IDH positive; 167 IDH negative). A fully adaptive Bayesian method was applied to calculate leakage-corrected relative cerebral blood volume (rCBV) maps from the DSC raw data. Tumour boundaries were manually defined and co-registered to the rCBV maps. The texture features were calculated based on the rCBV findings within the defined tumour. A 2-fold cross-validation setting of 1000 iterations using support vector machine and multinomial ordinal regression was applied to assess the predictive power of the extracted features in IDH phenotyping.

Results

The proposed rCBV analysis for IDH status stratification showed a sensitivity rate of 75% and specificity rate of 88%. In the non-parametric Wilcoxon test nine out of the ten classical histogram statistics and 12 texture features appeared significantly different across mutation status (p < 0.02). The distance error (difference between the real and predicted grade) was used to show the classification across grading: In 90.2 % of the cases the same features led to inferior or equal to 1 in and in 71.3% of cases to an exact prediction.

Conclusions

These promising preliminary results for DSC-MRI-based glioma stratification with respect to their IDH mutation status suggest further exploration into the potential diagnostic and predictive and predictive value of rCBV analysis as surrogate non-invasive biomarker for IDH classification of gliomas.

Legal entity responsible for the study

University College London.

Funding

Has not received any funding.

Disclosure

D. Roettger: Head of Scientific and Medical Affairs: IAG. All other authors have declared no conflicts of interest.

Collapse
Proffered Paper session - CNS tumours Proffered Paper session

Invited Discussant 373O, 374O and 375O

Lecture Time
17:15 - 17:30
Speakers
  • Martin J. Van den Bent (Rotterdam, NL)
Location
Hall B3 - Room 20, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30