Researchers from the Medical Faculty of Heidelberg, the German Cancer Research Center (DKFZ) and the National Center for Tumor Diseases (NCT) Heidelberg have investigated the efficacy of targeted drugs in newly diagnosed glioblastoma in the multicenter Phase 1/2 study “NCT Neuro Master Match (N2M2)”. The study, published in “Nature Medicine”, shows that the active ingredient temsirolim, already used in kidney cancer, achieves positive results. It proves that molecularly targeted therapy can be implemented quickly and efficiently.

Glioblastomas are highly aggressive, incurable brain tumors with an average survival time of about twelve months. Standard therapies consisting of surgery, radiation and chemotherapy with temozolomide prolong life by only a few months. Temozolomide fails in two-thirds of patients due to genetic resistance, which is why new therapeutic approaches are urgently needed.

The study included 228 patients with temozolomide-resistant glioblastoma. Molecular analyses of the tumor tissue, carried out within an average of 26 days, enabled precise drug selection by a molecular tumor board. Patients with an overactive mTOR pathway received temsirolim, which inhibits this pathway. Others received immunotherapies or standard therapy, always combined with radiation therapy.

Temsirolimus showed progression-free survival of at least six months in 39.1 percent of the 46 patients in this group, compared to 18.5 percent in the standard therapy group. The median survival time was 15 months, about three months longer than with standard therapy. These results mark an important step forward for patients without effective treatment options.

The study shows that precision medicine approaches are feasible in the initial treatment of glioblastoma without delaying radiation therapy. Temsirolimus and similar active ingredients could be established as standard therapy in the future. Further research is expected to clarify the effectiveness of other drugs to further improve the treatment of these aggressive tumors.

Original Paper:

Wick W, Dettmer S, Berberich A, et al. N2M2 (NOA-20) phase I/II trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed non-MGMT hypermethylated glioblastoma. Neuro Oncol. 2019; 21(1):95-105. doi:10.1093/neuonc/noy161

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New approach against glioblastomas: Researchers decipher immune regulation – MedLabPortal

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