ROAR trial: which treatment is effective after progression?

We read the Article by Patrick Y Wen and colleagues with great interest. 1 Wen PY Stein A van den Bent M et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol. 2022; 23: 53-64 Google Scholar Relapses of glial tumours are quite aggressive. The high objective response rates of patients in the interim results of this phase 2 study, which included patients with relapsed BRAFV600E mutation-positive low-grade and high-grade glioma and after standard multimodal therapy, are promising for clinicians working in the neuro-oncology field. The median overall survival in patients with glioblastoma was 13·7 months (95% CI 8·4–25·6), which is quite remarkable because survival times in patients with relapsed disease are often limited to only a few months. However, we are concerned about the discrepancy between median progression-free survival and median overall survival with the dabrafenib–trametinib combination. Wen and colleagues reported that median progression-free survival was 2·8 months (95% CI 1·8–13·7) with the dabrafenib–trametinib combination for patients with recurrent glioblastoma. The median overall survival duration (13·7 months) is almost five times that of median progression-free survival, and Wen and colleagues suggested that this difference might be related to the use of the dabrafenib–trametinib combination beyond progression. However, when the results were evaluated, only two patients stayed on dabrefinib–trametinib treatment beyond progression. Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trialDabrafenib plus trametinib showed clinically meaningful activity in patients with BRAFV600E mutation-positive recurrent or refractory high-grade glioma and low-grade glioma, with a safety profile consistent with that in other indications. BRAFV600E testing could potentially be adopted in clinical practice for patients with glioma. Full-Text PDF ROAR trial: which treatment is effective after progression? – Authors' replyWe thank Osman Sütcüoğlu and colleagues for their response to our Article on treatment with dabrafenib–trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma.1 Their Correspondence raises two points for discussion: the difference between median progression-free survival and median overall survival and the post-progression therapies in patients with gliomas, including glioblastoma after dabrafenib–trametinib treatment. Full-Text PDF