461P - Effectiveness of dabrafenib-trametinib and larotrectinib in adult recurrent glioblastoma patients: A real-life cohort analysis from 3 Italian centers

Background

Although less than 5% and 1.5% of glioblastomas (GBM) exhibit the BRAFV600E mutation and NRTK fusion, respectively, these cases are significant because some of these patients (pts) may respond well to BRAF/MEK and NTRK inhibitors. Given limited literature, this study aims to evaluate the efficacy of dabrafenib-trametinib and larotrectinib in treating adults with recurrent GBM.

Methods

We retrospectively analyzed a cohort of adult pts with recurrent GBM (WHO 2021) treated in 3 italian centers: Veneto Institute of Oncology (Padua), Ospedale Policlinico San Martino (Genoa), Ospedale del Mare (Naples). Molecular analysis was obtained on tissue samples with next-generation sequencing, PCR or immunohistochemistry. Dabrafenib-trametinib was given as part of compassionate use program or off-label, larotrectinib has an agnostic approval. Response assessment followed RANO criteria.

Results

Between 03-2020 and 11-2023, 17 GBM pts received target therapy: 13 with dabrafenib-trametinib, 4 with larotrectinib. 12 pts had ECOG PS 0-1. All had prior radiotherapy and temozolomide. Median line of therapy was 2 (range 2-4), with a median of 6 cycles (range 1-48) of treatment. As of 04-2024, median follow-up was 7.6 months. Median overall survival and progression-free survival (PFS) after starting therapy were 8.8 and 2.8 m, respectively. Dabrafenib-trametinib subgroup showcased the longest median PFS (5.09 m), a notable disease control rate (DCR) of 77% and an objective response rate of 30.7%. Among the 13 pts included, 9 had died while 3 pts are presently undergoing treatment. Pts treated with larotrectinib exhibited a shorter median PFS (2.5 m), with a DCR of 50%; no patient reported a response. 3/4 pts had passed away, one pt is currently continuing larotrectinib. No grade 3-4 adverse events were observed in either subgroup; in any case target therapy was interrupted for toxicity.

Conclusions

Our findings support dabrafenib-trametinib for BRAFV600E mutant GBM patients. Larotrectinib shows lower activity than in pediatric cases, suggesting further research is needed on larger groups to understand patient outcomes, molecular characteristics, prognostic factors, and treatment timing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.