BIOM-48. PTEN MUTATIONS PREDICT BENEFIT FROM TUMOR-TREATING FIELDS THERAPY IN PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract

Abstract BACKGROUND Glioblastoma IDH-wildtype (GBM-IDH-WT) recurs despite the standard of care which includes surgical resection and concurrent chemoradiotherapy. Optimal treatment for recurrent GBM-IDH-WT (rGBM) is not standardized and multiple therapeutic approaches are utilized. Clinical trials have shown that Tumor-Treating Fields (TTF) provide equal benefits compared to physician’s chemotherapy choice for patients with rGBM. However, not all rGBM patients respond equally to TTF and understanding which patients will benefit from TTF therapy is critical. METHODS We reviewed clinical, molecular, and outcome characteristics of rGBM patients between 09/2009 to 2/2019 in our institution. Patients who received TTF-treatment at the time of 1st recurrence were selected for analysis. Tumors were analyzed for mutations in 315 cancer-related genes by next-generation sequencing. Post-progression survival (PPS) defined as the interval from 1st recurrence to death or the time of analysis, was examined using the Log-rank test and multivariable Cox-regression model. RESULTS 149 rGBM patients were identified of which 29 (19%) were treated with TTF. Overall, no significant difference in survival was observed in rGBM patients who received TTF therapy (13.9-months vs 10.9-months, p= 0.06). However, among TTF-treated patients (n= 29), there was improved survival in PTEN-mutant (n= 14) patients compared to PTEN-wt (n= 15), (22.2-months vs 11.6- months, p= 0.017). No differences in TTF usage were observed between groups. Within the PTEN-mutant patients (70/149, 47%), those treated with TTF (n= 14) had longer PPS (22.2-months vs 9.3-months, p= 0.005). No survival benefit with TTF-treatment was observed in PTEN-wt patients (79/149, 53%). CONCLUSIONS Patients with GBM-PTEN-mutant tumors show a significant improvement in survival when treated with TTF at recurrence. Understanding the molecular mechanism underpinning the differences in response to TTF therapy could help elucidate the mechanism of action of TTF and identify patients that will benefit the most from this therapeutic option.