13 juni 2021: ASCO 2021

Hier een aantal aanbevolen abstracten over studies bij hersentumoren en kanker in centrale zenuwstelstel door artsen die werken voor ASCO zelf. Deze aanbevelingen doet Patrick Y. Wen MD. van het DANA-Farber Cancer Institute.

Klik op de nummers van de abstracten:

Clinical Science Symposium: Central Nervous System Tumors
Available Starting on Friday, June 4, 2021; 9:00 EDT

2009 First-in-human CAN-3110 (ICP-34.5 expressing HSV-1 oncolytic virus) in patients with recurrent high-grade glioma. EA Chiocca, I Solomon, H Nakashima, et al

Take-Home Message

  • This first-in-human study assessed the neurovirulence of CAN-3110, a malignant glioma cell–targeted, replication-efficient HSV-1–based oncolytic virus. Recurrent glioma patients received best standard-of-care treatment plus conservative dose-escalating, intratumorally delivered oncolytic virus.
  • Neither dose-limiting toxicity nor ICP-34.5–induced encephalitis or meningitis were observed; no treatment-associated adverse events were reported. Median overall survival was favorable (13.25 months), warranting more robust efficacy analyses. Immunologic and transcriptomic analyses are also underway.

Poster Discussion Session: Central Nervous System Tumors
Available Starting on Friday, June 4, 2021; 9:00 EDT

2013 Long-term results of the GEINO 1401 TRIAL: Randomizing patients to stop or to continue temozolomide until 12 cycles. M Domenech, C Fabregat-Franco, C Mesia, et al

Take-Home Message

  • This is a long-term results follow-up of the GEINO 1401 trial.
  • No benefit in terms of overall survival (18.2 months vs 22.0 months) or progression-free survival (61% and 62%) was observed with extended use (up to 12 cycles) of temozolomide in long-term survivor patients.

2014 Preliminary results of the abemaciclib arm in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A phase II platform trial using Bayesian adaptive randomization. EQ Lee, L Trippa, G Fell, et al

Take-Home Message

  • Preliminary results for the abemaciclib arm of the INSIGhT platform trial are reported.
  • Abemaciclib was safe, and no new adverse events were reported. Progression-free survival was extended (6.54 months vs 5.88 months), but overall survival was not improved compared with standard-of-care radiochemotherapy.

2015 Randomized phase 2 study of nivolumab (nivo) plus either standard or reduced dose bevacizumab (bev) in recurrent glioblastoma (rGBM). MS Ahluwalia, Y Rauf, H Li, e al

  • In this study, the ability of bevacizumab (an anti-VEGF antibody) to enhance limited nivolumab monotherapy activity in first-recurrent glioblastoma patients was assessed. Overall survival was improved in patients aged >60 years treated with nivolumab plus 10 mg/kg–dose bevacizumab compared with those treated with nivolumab plus 3 mg/kg–dose bevacizumab (at 1 year: 10.6 vs 5.9 months; P = .046) and in patients ≤60 years in both treatment arms (at 1 year: 8.0 vs 12.4 months; P = .90). Mild grade 1–2 toxicities and some non-neurological grade 3–4 adverse events were reported.
  • Overall, the addition of anti-VEGF therapy did not improve nivolumab activity; however, older patients may gain limited benefit.

2024 Multi-center, single arm phase II study of the dual mTORC1/mTORC2 inhibitor vistusertib for patients with recurrent or progressive grade II-III meningiomas. SR Plotkin, P Kumthekar, PY Wen, et al

 Take-Home Message

  • In this phase II study, the effects of dual mTORC1/mTORC2 inhibition on grade 2–3 meningioma progression were evaluated. PFS-6 was 51.5% with vistusertib 125 mg for 2 consecutive days/week in patients with progressive or recurrent meningiomas. Adverse events were tolerable.
  • Vistusertib treatment exceeded the Response Assessment in Neuro-Oncology (RANO)–identified PFS-6 rate of >35%, indicating activity in this difficult-to-treat population.

Oral Abstract Session: Central Nervous System Tumors
Monday, June 7, 2021; 8:00 AM–11:00 AM EDT

2000 Alliance A071601: Phase II trial of BRAF/MEK inhibition in newly diagnosed papillary craniopharyngiomas. PK Brastianos, E Twohy, SM Geyer, et al

Take-Home Message

  • In this phase II trial, newly diagnosed papillary craniopharyngioma patients without prior radiation and with BRAF mutations were treated with oral vemurafenib plus cobimetinib in 28-day cycles. Of the evaluable patients, 15/16 had a response to therapy (93.75%), and tumors were reduced by 83% (range, 52% to 99%). Treatment was discontinued in 4 patients due to adverse events.
  • Vemurafenib plus cobimetinib shows promise as a treatment option for patients with previously untreated papillary craniopharyngioma. Additional studies are proposed for assessing efficacy following radiotherapy. Toxicity may be a concern.

2002 Efficacy and safety of larotrectinib in adult and pediatric patients with tropomyosin receptor kinase (TRK) fusion-positive primary central nervous system tumors. S Perreault, CM van Tilburg, B Geoerger, et al

Take-Home Message

  • In this study, patients harboring tropomyosin receptor kinase (TRK) fusion–positive central nervous system tumors were treated with the TRK inhibitor larotrectinib. The objective response rate in all patients was 30%, and the overall 24-week disease control rate was 73%. Tumors were reduced in 82% of patients, and the median progression-free survival was 18.3 months. Neither the duration of response nor overall survival was reached. Grade 3–4 treatment-related adverse events were reported in 9% of patients; no patient discontinued treatment due to them.
  • Larotrectinib was safe and well-tolerated in patients with TRK fusion–positive central nervous system tumors, eliciting durable responses and a high disease control rate.

2004 EORTC 1709/CCTG CE.8: A phase III trial of marizomib in combination with temozolomide-based radiochemotherapy versus temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma. P Roth, T Gorlia, JC Reijneveld, et al

Take-Home Message

  • In this phase III EORTC 1709/CCTG CE.8 trial, the ability of marizomib to enhance the effects of temozolomide-based radiochemotherapy was evaluated in newly diagnosed glioblastoma patients.
  • Marizomib did not impact overall or progression-free survival, but it was associated with an increase in toxicity compared with the group receiving standard therapy.

2006 Evaluating the benefit of adaptive randomization in the CC-115 arm of the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A phase II randomized Bayesian adaptive platform trial in newly diagnosed MGMT unmethylated glioblastoma. R Rahman, L Trippa, G Fell, et al

Take-Home Message

  • In this phase II Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial, the activity of CC-115 was evaluated in newly diagnosed patients with MGMT unmethylated glioblastoma. No significant benefit in terms of PFS or OS was observed, and 58% of patients reported possible treatment-related CTCAEs compared with the control group.
  • Adaptive randomization facilitated a more efficient testing of the treatment, but no improvement in patient outcomes was observed.

2007 Olaparib in recurrent IDH-mutant high-grade glioma (OLAGLI). F Ducray, M Sanson, OL Chinot, et al

Take-Home Message

  • In this study, the efficacy of olaparib 300 mg twice daily was assessed in patients with recurrent high-grade IDH-mutant gliomas after radiotherapy and at least one line of alkylating chemotherapy. PFS-6 was 31%; at 11 months, 86% of patients had stopped treatment due to progressive disease. No patient definitively stopped treatment due to adverse events.
  • Olaparib was well-tolerated but had limited activity in recurrent IDH-mutant glioma.

2008 Impact of mutant IDH (mIDH) inhibition on DNA hydroxymethylation, tumor cell function, and tumor immune microenvironment (TIME) in resected mIDH1 lower-grade glioma (LGG). M Lu, TF Cloughesy, PY Wen, et al

Take-Home Message

  • In this study, resection-eligible patients with mutant IDH1 lower-grade glioma with recurrent non-enhancing tumors received ivosidenib 500 mg once daily/250 mg twice daily, vorasidenib 10/50 mg once daily, or no treatment for 4 weeks before surgery. Both vorasidenib and ivosidenib elicited optimal D-2-hydroxyglutarate (2-HG) suppression (90% and 50% of patients, respectively), which was correlated with upregulated neural differentiation–related, type I interferon signaling and antigen presentation gene expression and downregulated stemness-related gene expression. T-cell proliferative markers were decreased in 2-HG–suppressed tumors, while 5-hydroxymethylcytosine and CD3+ and CD8+ tumor–infiltrating lymphocyte levels were increased.
  • The tumor-intrinsic and -extrinsic mechanisms associated with 2-HG suppression identified in this study suggest a role for vorasidenib in combination immunotherapy.

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