CTNI-59. TUMOUR VOLUMES PREDICT PROGNOSIS AND RESPONSE TO TREATMENT WITH DEPATUXIZUMAB MAFADOTIN

Abstract BACKGROUND Preclinical data demonstrates that tumor volumes predicted response to the anti-EGFR ADC Depatuxizumab mafadotin (Depatux-M) because of reduced drug delivery in large tumors. We investigated the impact of tumor volumes on outcomes with Depatux-M in the EORTC randomized phase 2 Intellance 2 study on recurrent glioblastoma (NeuroOncol 22(5):684). METHODS 260 patients were randomized to Depatux-M, Depatux-M with temozolomide, or control treatment (lomustine/temozolomide). Manual segmentation of enhancing tumor on baseline MRI scans was performed and compared with OS and PFS using SPSS Version 29.0: Kaplan-Meier survival analysis including log rank test and Cox regression analyses; categorical data were compared with Fishers’ exact test; correlation between 2D and 3D measurements with Pearson’s correlation. RESULTS MRI scans and data from 240/260 (92%) patients were available. Firstly, we confirmed that tumor volumes were a significant prognostic variable. Significant differences were seen in OS between the 0-20 vs 20-40 ml groups (321 vs 216 days, p<0.001) and between the 20-40ml vs 40+ groups (216 vs 150 days, p<0.001) with corresponding differences in PFS. Tumor volumes were also predictive of benefit from Depatux-M, with only patients with smaller tumors benefiting from Depatux-M. Patients in the 0-20 ml and 20-40 ml group group had superior OS when treated with Depatux-M compared to controls (356 vs 309 days, p=0.011 and 229 vs 178 days, p=0.028 respectively). Conversely, the 40 ml + group had no benefit (146 vs 152 days, p=0.875) as predicted. The benefit was maximal in the combination arm, with OS improvement in the 0-20 ml group (437 vs 309 days, p=0.007) and 20-40ml groups (225 vs 178 days, p=0.009). The impact of tumor volumes was confirmed in multi-variate analysis and superior to similar analysis with 2D RANO measurements. CONCLUSIONS Tumor volumes are an important prognostic variable in recurrent glioblastoma and modulate survival to large molecules like Depatux-M.