Discussing Immunotherapies and Targeted Therapies in Brain Cancer

Patrick Wen, MD, professor of Neurology at Harvard Medical School and director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute, discusses the evolution of treating patients with brain cancer with immunotherapies and targeted therapies.

Immunotherapies and targeted therapies have improved survival outcomes and shown that they are active for patients with glioma. Previously, it was thought these kinds of targeted therapies wouldn’t work for patients with a glioblastoma, but according to Wen, a small subset of patients with glioblastoma have shown BRAF V600E mutations have responses to treatments like dabrafenib (Tafinlar) and trametinib (Mekinist) that are approved for different subtypes.

The evidence for these inhibitor combinations has allowed clinicians to think differently about what mutations are active in glioblastoma and how to target them appropriately. For instance, looking for NTRK fusions in glioblastoma has led to emerging evidence that entrectinib (Rozlytrek) is active for these patients and that it is worth pursuing evidence for other inhibitors, like erdafitinib (Balversa). Wen explains how the evidence has led to more studies and the hope that over time they will be fruitful.

Transcription:

0:08 | I think for a long time, because of the issues of the blood brain barrier, heterogeneity, and redundancy of signaling pathways, there was thought that targeted therapies would never work for glioblastoma. But we have found that these small subsets of patients that do respond. Two percent of patients with glioblastoma that have BRAF V600E mutations have shown responses to the dabrafenib and trametinib, a BRAF and MEK inhibitor combination that's approved for melanoma.

0:42 | The response rate in glioblastoma is about 32%. In low-grade gliomas, it's 69%. Responses in both populations are durable, and it was part of a study with multiple tumors that led to the FDA approval for that combination for all solid tumors in 2022. There's also evidence that targeted therapies may be helpful for tumors with the very rare TRK fusions. Entrectinib seems to be active for gliomas with NTRK fusion. There's also emerging evidence that erdafitinib, an FGFR inhibitor, has activity in gliomas.