Researchers publish critical study on 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 drug in the journal Nature Reviews Clinical Oncology.

In the September 2024 issue, Dr. Stanislav Lazarev and Dr. Kunal Sindhu of 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) to treat brain tumors called IDH-mutated low-grade gliomas (LGGs).

Their research results raise considerable doubts about the approval process and the actual benefits of the drug for patients.

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

Dr. Lazarev and Dr. Sindhu examine the INDIGO trial, the clinical trial that supported the approval of vorasidenib. A major problem they highlight is the trial's comparative methodology. Rather than directly comparing vorasidenib to the current standard of care, chemoradiotherapy, it was tested against a placebo. This approach has raised ethical concerns because it resulted in some participants being deprived of an established and effective treatment.

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

The commentary suggests that while vorasidenib may slow disease progression, it offers no clear benefit in terms of prolonging life or improving patients' quality of life. This lack of proven benefit is concerning, especially given the high cost of the drug – nearly $500,000 annually.

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

The study challenges the assumption that vorasidenib is a better treatment option and suggests that established treatments should remain the first choice until further evidence demonstrates the effectiveness of the new drug.

For patients, the commentary underscores the importance of thoroughly discussing treatment options with the healthcare provider. Although vorasidenib is FDA-approved, its high cost and uncertain long-term benefits require careful consideration. Patients should be well informed about the potential risks and benefits before choosing this new treatment.

Dr. Lazarev and Dr. Sindhu call for several further steps. These include conducting more rigorous trials to directly compare vorasidenib with standard treatments, re-evaluating existing data from the INDIGO trial, and examining the drug's cost-effectiveness. In addition, updating treatment guidelines based on new evidence will ensure that healthcare practices are aligned with the most effective and ethical approaches.

This critical review underlines the need for sound evidence and ethical considerations when approving and introducing new treatments.