OS07.4.A Regorafenib in recurrent glioblastoma patients: a multicentric real-life study
Authors: Bruno F , Pellerino A , Pronello E , Palmiero R , Polo V , Vitaliani R , Trincia E , Internò V , Porta C , Soffietti R , Rudà R 
Published: September 2022

Abstract

Background
Few options are still available for recurrent glioblastoma (GBM). In the Italian phase 2 REGOMA trial, regorafenib improved overall survival, as compared to lomustine, for GBM patients at first progression after chemoradiation. Here, we present the results of a real-life multicentre study that analysed clinical and radiological features, response to treatments, tolerability, and outcome of a cohort of GBM patients treated with regorafenib at first tumour progression.

Patients and Methods
We enrolled GBM patients at first tumour progression in three Italian Institutions (Turin, Treviso, Bari). Regorafenib was administered following an escalation dose protocol (1st cycle: 80 mg/day for 2 weeks, then 120 mg/day for one week; 2nd cycle: 120 mg/day for 2 weeks, then 160 mg/day for one week; 160 mg/day from the 3rd cycle). MRI scans were obtained at baseline and every 3 months. Progression-free survival (PFS) and overall survival (OS) were defined as time from regorafenib initiation and disease progression or death.

Results
From January 2020 to January 2022, 66 GBM patients were included. Median age was 60.0 years. MGMTp methylation was found in 30 patients (45.5%). First-line treatment consisted in chemoradiation in 61 (92.4%), in upfront TMZ (3, 4.5%) or RT alone followed by TMZ (2, 3.0%). Median dose was 120 mg/day 21q28 day, which was lower than that used in REGOMA trial (149 mg). Median PFS (mPFS) was 2.7 months (2.4 - 3.0 95% CI) and median OS (mOS) 7.1 months (5.4 - 8.9 95% CI). Best RANO response to regorafenib was partial response (PR) in 10 (15.1%), stable disease in 14 (21.2%), and progressive disease in 42 (63.7%) patients. All PRs were observed within the first three months of treatment. Patients who completed treatment up the 6th, 9th, and 12th cycles were 20, 3 and 2, respectively. Forty-six (69.7%) patients presented adverse events of any grade, and 21 (31.8%) grade III-IV toxicity. The most frequent adverse events were fatigue (33.3%), hand-foot syndrome (27.3%), and liver enzymes increase (15.2%). Two patients only (3.0%) interrupted regorafenib due to toxicity.In a multivariable analysis, factors significantly associated with disease progression were higher age (p = 0.035) and absence of MGMTp methylation (p = 0.024).

Conclusion
In this real-life study on 66 patients, mPFS and mOS were similar to those of the 59 patients enrolled in the regorafenib arm of REGOMA trial (2.7 vs 2.0 months; 7.1 vs 7.4 months, respectively). However, we observed a higher rate of PRs as compared to REGOMA (15% versus 3.0%). Type and severity of adverse events were similar between the two studies. Moreover, we had a lower incidence of discontinuations of regorafenib due to toxicity, maybe attributable to the lower dose intensity.We are further analysing the data of MRI-perfusion, with the aim to explore whether it can predict an early response or progression in comparison to standard MRI.