Startseite Kongressberichte & Archiv 2021 ASCO Annual Meeting CNS Cancer Central Nervous System Tumors
Central Nervous System Tumors
Alliance A071601: Phase II trial of BRAF/MEK inhibition in newly diagnosed papillary craniopharyngiomas.
Priscilla Kaliopi Brastianos, Erin Twohy, Susan Michelle Geyer, et al.
The study authors conclude that Vemurafenib/cobimetinib showed an objective response in all patients who received 1 or more cycles of therapy. The data indicate that BRAF/MEK inhibitors could be a powerful tool in the treatment of previously untreated papillary craniopharyngioma. Clinical trial information: NCT03224767
Jessica Stiefel, Brian H. Kushner, Ellen M. Basu, et al.
Adult-onset Neuroblastoma is a rare disease and a therapeutic challenge. The authors mention enrichment of ALK mutations permits consideration of targeted therapy. ALK inhibitors are well tolerated and are often associated with significant responses. Treatment with serial ALK inhibitors led to ongoing benefits. The study authors conclude that ALK inhibitors should be considered for treatment in future Adult-onset Neuroblastoma.
Efficacy and safety of larotrectinib in adult and pediatric patients with tropomyosin receptor kinase (TRK) fusion-positive primary central nervous system tumors.
Sébastien Perreault, Cornelis Martinus van Tilburg, Birgit Geoerger, et al.
The study authors demonstrated that larotrectinib had rapid and durable responses in InTRK fusion-positive CNS tumors with a high disease control rate. Larotrectinib had a favorable safety profile. The authors conclude that these results support testing for NTRK gene fusions in patients of all ages with CNS tumors. Clinical trial information: NCT02637687, NCT02576431
The 1994 National Cancer Institute’s strategy to fund multi-institutional, multidisciplinary consortia to design and conduct early phase clinical trials in patients with high grade gliomas.
Stuart A. Grossman, Louis B. Nabors, Joy D. Fisher, et al.
The study authors conclude that therapeutic progress for high-grade gliomas has been slow for many reasons. The activities of the New Approaches to Brain Tumor Therapy (NABTT: 1994-2009) and Adult Brain Tumor Consortium (ABTC: 2009-2021) focused multidisciplinary, multi-institutional experts on major challenges unique to brain tumor research. Innovative early phase clinical studies rich in correlative endpoints were developed and research grants were fostered together with many other activities to explore novel treatment options for primary brain tumors.
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.
Patrick Roth, Thierry Gorlia, Jaap C. Reijneveld, et al.
The study authors conclude that adding marizomib - a novel, irreversible, and brain-penetrant pan-proteasome inhibitor - to standard radiochemotherapy did not improve overall and progression-free survival in newly diagnosed glioblastoma. Clinical trial information: NCT03345095
Nader Sanai, Yu-Wei Chang, Tigran Margaryan, et al.
The study authors show that Abemaciclib and LY3214996 - a selective ERK1/2 inhibitor - achieve pharmacologically relevant concentrations in Gd-non-enhancing GBM tissue. They are associated with suppression of the RB pathway and tumor proliferation. The Optimal Time Interval (OTI) for tissue sampling was 3-5 hours after the final drug dose after 6 days of presurgical drug exposure. Clinical trial information: NCT04391595
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.
Rifaquat Rahman, Lorenzo Trippa, Geoffrey Fell, et al.
The study authors conclude that this trial facilitated more efficient testing of CC-115. It decreased the number of patients allocated to the CC-115 arm relative to a standard randomization design. Clinical trial information: NCT02977780
Francois Ducray, Marc Sanson, Olivier L. Chinot, et al.
The study authors conclude that olaparib monotherapy was well tolerated and resulted in some activity. This supports its evaluation in association with alkylating chemotherapy in recurrent IDH-mutant gliomas. Clinical trial information: NCT03561870
Impact of mutant IDH (mIDH) inhibition on DNA hydroxymethylation, tumor cell function, and tumor immune microenvironment (TIME) in resected mIDH1 lower-grade glioma (LGG).
Min Lu, Timothy Francis Cloughesy, Patrick Y. Wen, et al.
The study authors suggest according to their data, that both tumor-intrinsic and -extrinsic mechanisms underlie 2-HG suppression by vorasidenib and ivosidenib. Vorasidenib - an oral, brain-penetrant, dual inhibitor of mIDH1/2 -, and to a lesser extent ivosidenib - a first-in-class oral inhibitor of mIDH1-, increased 5-Hydroxymethylcytosine (5hmC), promoted cellular differentiation, and inhibited tumor cell proliferation; interestingly, both also increased T-cell infiltration. Interferon signaling was activated, and antigen presentation capability increased. The authors recommend the development of vorasidenib in combination with immunotherapy. Clinical trial information: NCT03343197