P17.06.B TARGETED THERAPY MATCHED TO GENOMIC ALTERATIONS (BRAFV600E, NTRK, FGFR, ROS1, PIK3CA, PTEN) IN PATIENTS WITH RECURRENT IDH WILDTYPE GLIOBLASTOMA: A REAL-LIFE COHORT ANALYSIS FROM VENETO INSTITUTE OF ONCOLOGY, PADUA (ITALY)
Authors: Padovan M , De Toni C , Maccari M , Bosio A , Cerretti G , Caccese M , Corrà M , Vizzaccaro S , Cestonaro I , Pittaro A , Guerriero A , Coppola M , Lombardi G 
Published: September 2023

Abstract

BACKGROUND
The use of next-generation sequencing (NGS) allows the identification of subgroups of patients that may respond to personalized targeted therapies (TT). Despite the acquired deep knowledge about biology, there are only a few data available regarding TT efficacy and feasibility for patients with glioblastoma (GBM).

MATERIAL AND METHODS
We retrospectively analyzed a cohort of patients with recurrent GBM treated at Veneto Institute of Oncology, Padua (Italy) with TT based on their individual NGS profile. NGS was obtained with FoundationOne®CDx on formalin-fixed paraffin-embedded (FFPE) tissue samples. We identified 6 druggable genomic alterations, classified according to ESCAT (ESMO Scale for Clinical Actionability of molecular Targets): BRAFV600E mutation (IB), NTRK1-2-3 fusions (IC), FGFR1-2-3 alterations (IIB), ROS1 fusions (IIIA), PIK3CA mutations (IIIA) and PTEN loss/mutations (IIIA). TT was given as agnostic approval, part of compassionate use programs or in clinical trials. Response assessment was based on RANO (Response Assessment in Neuro-Oncology) criteria.

RESULTS
Between March 2020 and December 2022, 34 patients with recurrent glioblastoma received TT (19 males, 15 females, median age of 54 years at time of TT initiation). ECOG PS was 0-1 in 29 pts. All patients received radiotherapy and temozolomide as first-line therapy. The median line of therapy with TT was 3 (range 2-7). TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts). At data cut-off (March 2023), 19 patients had died. In the entire cohort, median overall survival and progression-free survival (PFS) after starting TT was 8.72 and 2.14 months, respectively. The dabrafenib/trametinib subgroup had the longest median PFS (5.23 months), a disease control rate (DCR) of 77%, an objective response rate of 22%, and a median duration of response of 22.5 months. 7/9 pt had died and 2 pts are continuing dabrafenib/trametinib. The pt with ROS1-GOCP fusion maintained a complete response for 12 months with entrectinib. Among the others, no complete/partial responses were detected. DCR due to stable disease was 50% in larotrectinib and erdafitinib, 8.3% in ipatasertib+/-atezolizumab, 0% in alpelisib subgroup. No toxicities were reported in dabrafenib/trametinib subgroup. Among all patients, no grade 4 drug-related adverse events were observed and in any case TT was interrupted for toxicity.

CONCLUSION
Our results confirm the activity of dabrafenib/trametinib in BRAFV600E mutant glioblastoma pts and might suggest deeper explorations in targeting ROS1 and FGFR. Further correlation among patients' outcome, molecular characteristics and TT timing are still under investigation.