Impact of a molecular prescreening program (MPP) in the management of patients with non-glioblastoma brain tumors

Abstract

Background: Although patients(pts) with low-grade gliomas and anaplastic tumors have better outcomes than those with glioblastoma, most pts that relapse will die as a consequence of their disease. There is an unmet clinical need for new treatments in this population. Methods: Between 2014-2017, 145 pts with brain tumors were evaluated in the Early Drug Development Unit at Vall d'Hebron Institute of Oncology and included in our MPP. Clinical and molecular data from 36 pts (24%) with non-glioblastoma diagnosis were retrospectively reviewed. Results: Median age at diagnosis was 33 years. The majority were low-grade tumors (62.2%) with astrocytic differentiation (51.4%). Most pts (78.4%) were initially treated in other institutions (78%) with a median time since diagnosis to referral of 60.6 months (CI95%). Most pts (81%) were temozolomide-refractory. Molecular profiling identified a potentially targetable alteration in 78% of the cases. This included IDH mut (54%), PIK3CA/PTEN mut (16%), EGFR fusion (5%) and FGFR mutation/fusions (5%) and BRAF mutations/translocations(5%). Eleven cases (29%) were enrolled in phase 1 clinical trials and 4 (11%) in molecularly matched clinical trials (2 IDH inhibitor, 2 FGFR inhibitor). One patient with a IDH1132H mut treated with a IDH inhibitor achieved a stable disease >10 months and another with FGFR1 E17-TACC1 translocation has an ongoing partial response lasting over 6 months. Median overall survival (OS) since the referral to our unit was of 32 weeks (CI95%18 to 45), 78% survived at least 12 weeks and only 4 died during the first month(11,1%). Pts enrolled in matching trials had numerically better survival than those who entered unmatched trials (44 vs 22 weeks, p=0,131). Conclusions: Although rare, the high presence of drugable mutations and the lower likelihood of early death compared to glioblastoma makes them an interesting target for molecular prescreening and inclusion in phase I clinical trials.