Regorafenib for recurrent high-grade glioma: a unicentric retrospective analysis of feasibility, efficacy, and toxicity

Abstract

We describe here 11 consecutive patients with recurrence of high-grade glioma treated with regorafenib at our university medical center. The majority of patients had MGMT promoter methylation (9/11 cases). Regorafenib was given as 2nd line systemic treatment in 6/11 patients and 3rd or higher line treatment in 5/11 patients. The median number of applied cycles was 2 with dosage reductions in 5/11. Response to treatment was observed in 4/11 (PR in 1/11, and SD in 3/11). Median overall survival for the cohort was 16.1 months, median progression-free survival 9.0 months, and median time to treatment failure 3.3 months. Side effects of any CTCAE grade were noted in all patients, hereby 6/11 with CTCAE °III-IV reactions. High-grade side effects were of dermatologic, cardiovascular, and hematologic nature. A mean treatment delay of 57.5 days (range 23–119) was noted between tumor board recommendation and treatment initiation due to the application process for off-label use in this indication. In conclusion, treatment with regorafenib in relapsed high-grade glioma is a feasible treatment option but has to be considered carefully due to the significant side effect profile.

Observational real-life study on regorafenib in recurrent glioblastoma: does dose reduction reduce toxicity while maintaining the efficacy?

“…We reported a lower rate of adverse events of any grade (69.7%) according to CTCAE v5.0 as compared with other real-life studies (90.7% -100.0%). 23,24,27 Similarly, we observed a lower rate of adverse events grade 3-4 (31.8%) compared with other series (53.0% -83.3%). 24,27,28 Furthermore, we reported a reduced incidence of some adverse events that were described as frequent complications in other studies: for example, the incidence of liver enzymes elevation was lower in our series than in REGOMA trial (15.2% vs 48.0%), as well as that of hypertension (12% vs 22%), low platelet count (10.6% vs 20.0%), hypothyroidism (12.1% vs 19.0%), or increased pancreatic enzymes (4.5% vs 20.0%); on the other hand, we reported a higher incidence of fatigue (33.3% vs 24.0%) and a similar incidence of hand-foot syndrome (27.3% vs 22.0%) as compared with REGOMA.…”

“…12 Patients with GBM IDH-mutant were 5/54 (9.3%) in the observational real-life trial from Lombardi et al, 23 whereas other retrospective studies included more heterogeneous cohorts of patients with both GBM IDH-wildtype and lower-grade gliomas IDH-mutant. [24][25][26][27][28] In our study, we employed for the rst time a dose escalation protocol to improve patient tolerability and compliance. We reported a lower rate of adverse events of any grade (69.7%) according to CTCAE v5.0 as compared with other real-life studies (90.7% -100.0%).…”

“…In fact, the mPFS from our study (2.7 months) was similar to that reported in REGOMA trial (2.0 months) and other studies (2.1 -3.5 months). [23][24][25][26][27][28] Noteworthy, mPFS spans in a quite narrow gap (2-3.5 months) across different studies, which probably mirrors the fact that the time from regorafenib initiation to rst MRI assessment (commonly after 2-3 cycles, depending on the investigator's schedule) often becomes a surrogate for time-to-progression, being PD the most common RANO response to regorafenib (from 50% to 100% of cases -Table 5).…”

“…Recently, some real-life trials showed similar impact on survival but a higher rate of adverse events than in REGOMA, thus raising concerns over tolerability. [23][24][25][26][27][28] The aim of this observational study designed in 2019 was to assess the e cacy and tolerability of a lower intensity regorafenib regimen in a real-life cohort of GBM patients at rst progression.…”

Antiangiogenic Therapy for Malignant Brain Tumors: Does It Still Matter?

“…Of note, the OS of patients treated with lomustine from REGOMA trial was remarkably short (5.6 months) as compared with that of patients included in the lomustine single arms of other randomized controlled trials (median OS 7.1-10.4 months [5,72,73], which could imply an overestimation of regorafenib efficacy. Few other studies have shown similar impact on survival [74][75][76][77][78][79], but a higher rate of adverse events than in REGOMA, thus raising concerns over tolerability. A lower intensity regimen proved as effective as the standard 160 mg daily schedule used in REGOMA trial (median PFS and median OS of 2.0 months and 7.4 months), but with lower adverse events [80].…”