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.
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.
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).
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.
Clinical trial identification
Legal entity responsible for the study
Vall d'Hebron Institute of Oncology (VHIO).
Has not received any funding.
J. Carles: Speaker bureau: Bayer, Janssen; Advisor committee: BMS, MSD, Janssen, Astellas, Pfizer. E. Garralda: Advisory role: Roche, NeoMed Therapeutics, Ellypses Pharma. All other authors have declared no conflicts of interest.