Researchers publish critical examination of new brain tumor drug

Two researchers from the Icahn School of Medicine at Mount Sinai recently published their critical evaluation of a new brain tumor medicine in the journal Nature Reviews Clinical Oncology.

In the September 2024 issue, Stanislav Lazarev, MD, and Kunal Sindhu, MD, from Mount Sinai’s Department of Radiation Oncology, offer a thorough critique of vorasidenib, a new drug recently approved by the Food and Drug Administration (FDA) for treating brain tumors called IDH-mutant low-grade gliomas (LGGs).

Their research raises significant concerns about the approval process and the drug’s actual benefits for patients.

LGGs are a type of brain tumor that has mutations in the isocitrate dehydrogenase (IDH) genes, which are important in the development and progression of these cancers. LGGs are typically slow-growing tumors that can affect brain function depending on their location. Vorasidenib is aimed at patients with these specific genetic mutations, offering a targeted treatment approach.

Drs. Lazarev and Sindhu scrutinize the INDIGO trial, the clinical study that supported vorasidenib’s approval. One major issue they highlight is the trial’s comparison methodology. Instead of comparing vorasidenib directly with the current standard treatment, chemoradiotherapy, it was tested against a placebo. This approach has raised ethical concerns, as it involved withholding an established and effective treatment from some participants.

Another critical point made is the lack of evidence showing that vorasidenib improves overall survival or quality of life compared to existing therapies.

The commentary suggests that while vorasidenib may slow disease progression, it does not offer clear benefits in terms of extending life or enhancing patients’ quality of life. This absence of demonstrated benefit is concerning, especially given the drug’s significant cost—nearly $500,000 annually.

The implications of this commentary are profound for both clinicians and patients. For health care providers, the findings emphasize the need to carefully evaluate new treatments before adopting them as standard practice.

The study challenges the assumption that vorasidenib is a superior option, suggesting that established treatments should remain the primary choice until further evidence supports the new drug’s efficacy.

For patients, the commentary underscores the importance of discussing treatment options thoroughly with health care providers. Although vorasidenib is FDA-approved, its high cost and uncertain long-term benefits warrant cautious consideration. Patients should be well-informed about the potential risks and benefits before opting for this new treatment.

Drs. Lazarev and Sindhu call for several next steps. They include conducting more rigorous trials to compare vorasidenib directly with standard treatments, reassessing the existing data from the INDIGO trial, and investigating the cost-effectiveness of the drug. Additionally, updating treatment guidelines based on new evidence will ensure that health care practices are aligned with the most effective and ethical approaches.

This critical review highlights the need for robust evidence and ethical considerations in the approval and adoption of new treatments.