Abstract 380P
Background
PCNS pts are under-represented in early clinical trials. We aimed to describe the characteristics and outcomes of the VHIO-UITM cohort and develop tools to optimize pt selection.
Methods
Of all referrals between 2010 to 2019, subset of 141 pts considered eligible was retrospectively studied. Patient data, pathological characteristics, OS and PFS data were collected and analyzed.
Results
Median age 46 y (range 21-75), 59.6% male, ECOG 0/1 28.3%/71.6% , 57.4% glioblastoma, 25.5% low-grade glioma, 12.8% grade 3 gliomas, median of 2 prior therapies (range 0-8), including chemoradiation (70%), bevazicumab (50%) and secondary resection (41%); 45% were using steroids. Median time from diagnosis to first VHIO-UITM visit was 3.2 years (CI95% 2.28-4.31). 49.6% were treated in dose escalations, 23.4% in dose expansion/baskets, 26.9% were not enrolled, (due to lack of promising molecular target (36%), lab abnormality (28%, mostly thrombocytopenia) or clinical deterioration (14%)). Pts received targeted agents (74%), immunotherapies (9%), epigenetic modulators (4%). Median PFS was 2.3 months (2.0- 3.1), PFS>1 year was seen in 13.3% of cases, but most (75%) had clinical or radiological progression as best response. Median OS was 5.0 months (4.2-6.2), with 28% dying within 12 weeks. NGS based enrichment was used in 32%: MET (8.5%), NOTCH (8.5%), IDH (7.1%), SMO (2.8%), FGFR (2.8%), BRAF (2.8%) NTRK(2.8%). Pts with matched targeted treatment had a median PFS of 2.2 months vs. 2.3 unmatched population (HR 1.2, 95% CI (0.72-1.72), p=0.60). Using the LASSO selection method we generated a prognostic model for PFS with a 67% c-index including ECOG, grade, extent of resection, antecedent of chemoradiation, number of previous progressions and systemic therapies, antiepileptic use and neutrophil count.
Conclusions
pCNS pts referred to VHIO-UITM tend to be young, have a good PS despite being pretreated. Screening failure rates are comparable to pts with other primary tumors, but a higher early mortality rate is seen. Clinical benefit is over 10%, without impact of molecular enrichment on PFS. Clinicopathological and laboratory factors are could be relevant predictors of outcome in this population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Vieito Villar: Advisory/Consultancy: Debio; Advisory/Consultancy: Roche; Advisory/Consultancy: TFS; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Merck-Serono. A.B. Azaro Pedrazzoli: Advisory/Consultancy: Orion Pharma; Advisory/Consultancy: Amcure GmbH. I. Braña: Advisory/Consultancy: Orion Pharma; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Serono; Advisory/Consultancy: Rakutan Pharma; Speaker Bureau/Expert testimony: Roche. M. Gonzalez: Advisory/Consultancy: Roche; Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Pand Lilly. O. Saavedra Santa Gadea: Travel/Accommodation/Expenses: KYOWAKIRIN; Travel/Accommodation/Expenses: MSD. V. Galvao de Aguiar: Travel/Accommodation/Expenses: F Hoffman la Roche. A. Hernando-Calvo: Travel/Accommodation/Expenses: Kyowa Kirin. J. Carles: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Johnson & Johnson; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas Pharma; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZéneca; Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: AstraZéneca. R. Dienstmann: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Sharp & Dohme; Research grant/Funding (self): Merck; Research grant/Funding (institution): Pierre Fabre. E. Garralda: Research grant/Funding (institution): Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche ; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Thermo Fisher; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: F.Hoffmann/La Roche; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Neomed Therapeutics; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Janssen Global Services; Advisory/Consultancy: SeaGen; Advisory/Consultancy: TFS; Advisory/Consultancy: Alkermes; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Mayers Squibb; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Menarini; Travel/Accommodation/Expenses: Glycotope. All other authors have declared no conflicts of interest.