Salvatore Grisanti1, Vittorio D Ferrari2, Michela Buglione3, Giorgio M Agazzi2, Roberto Liserre4, Luigi Poliani5, Luciano Buttolo6, Stefano Gipponi7, Rebecca Pedersini2, Francesca Consoli2, Pierpaolo Panciani6, Elisa Roca2, Giannantonio Spena6, Luca Triggiani3, Alfredo Berruti2. 1. Department of Medical Oncology, Spedali Civili di Brescia and University of Brescia, Brescia, Italy - salvatore.grisanti@tin.it. 2. Department of Medical Oncology, Spedali Civili di Brescia and University of Brescia, Brescia, Italy. 3. Department of Radiation Oncology, Spedali Civili di Brescia and University of Brescia, Brescia, Italy. 4. Department of Neuro-Radiology, Spedali Civili di Brescia and University of Brescia, Brescia, Italy. 5. Department of Pathology, Spedali Civili di Brescia and University of Brescia, Brescia, Italy. 6. Department of Neuro-Surgery, Spedali Civili di Brescia and University of Brescia, Brescia, Italy. 7. Department of Neurology, Spedali Civili di Brescia and University of Brescia, Brescia, Italy.
Abstract
INTRODUCTION: Second line treatment of recurrent or progressive glioblastoma multiforme (GBM) is not standardized. Anti-angiogenic strategies with tyrosine-kinase inhibitors have been tested with conflicting results. We tested the association of sunitinib plus irinotecan (CPT-11) in a phase II trial in terms of response rate (RR) and 6-months progression-free survival (6-PFS). We also reviewed the clinical evidence from all the trials with sunitinib in this setting published to date and summarized it in a meta-analysis. EVIDENCE ACQUISITION: Patients with GBM recurrent or progressive after surgery and standard chemo-radiotherapy were treated with sunitinib 37.5 mg/day for 14 days + CPT-11 125 mg/sqm every 14 days in a Simon's two-stage phase II study. A summary data meta-analysis was performed to establish the 6-PFS in patients with ascertained histological diagnosis of GBM treated with sunitinib. EVIDENCE SYNTHESIS: Six patients were enrolled in the stage I of the trial and only one had a stable disease. The overall response rate was 17% and 6-PFS was not reached. Therefore, the trial was stopped early for insufficient activity. All toxicities were grade 1-2. Systematic review of the literature identified 9 studies (including the present one) for a total of 221 patients. Pooled 6-PFS was 15.1% (95% CI: 9.0-24.4). Subgroup analysis by different schedule revealed a 6-PFS of 17.5% (95% CI: 10.3-28.1) in the weekly setting which was consistent across all the studies (I2=0%, P=0.66) and a pooled 6-PFS of 12.7% (95% CI: 4.9-29.1) in the daily setting with a substantial amount of heterogeneity (I2=65%, P=0.01). CONCLUSIONS: Results of this trial and those of the systematic review indicate that, compared to conventional chemotherapy or bevacizumab, sunitinib has insufficient activity in the setting of recurrent GBM. Better patient's molecular stratification for second-line treatment in GBM is warranted.
INTRODUCTION: Second line treatment of recurrent or progressive glioblastoma multiforme (GBM) is not standardized. Anti-angiogenic strategies with tyrosine-kinase inhibitors have been tested with conflicting results. We tested the association of sunitinib plus irinotecan (CPT-11) in a phase II trial in terms of response rate (RR) and 6-months progression-free survival (6-PFS). We also reviewed the clinical evidence from all the trials with sunitinib in this setting published to date and summarized it in a meta-analysis. EVIDENCE ACQUISITION: Patients with GBM recurrent or progressive after surgery and standard chemo-radiotherapy were treated with sunitinib 37.5 mg/day for 14 days + CPT-11 125 mg/sqm every 14 days in a Simon's two-stage phase II study. A summary data meta-analysis was performed to establish the 6-PFS in patients with ascertained histological diagnosis of GBM treated with sunitinib. EVIDENCE SYNTHESIS: Six patients were enrolled in the stage I of the trial and only one had a stable disease. The overall response rate was 17% and 6-PFS was not reached. Therefore, the trial was stopped early for insufficient activity. All toxicities were grade 1-2. Systematic review of the literature identified 9 studies (including the present one) for a total of 221 patients. Pooled 6-PFS was 15.1% (95% CI: 9.0-24.4). Subgroup analysis by different schedule revealed a 6-PFS of 17.5% (95% CI: 10.3-28.1) in the weekly setting which was consistent across all the studies (I2=0%, P=0.66) and a pooled 6-PFS of 12.7% (95% CI: 4.9-29.1) in the daily setting with a substantial amount of heterogeneity (I2=65%, P=0.01). CONCLUSIONS: Results of this trial and those of the systematic review indicate that, compared to conventional chemotherapy or bevacizumab, sunitinib has insufficient activity in the setting of recurrent GBM. Better patient's molecular stratification for second-line treatment in GBM is warranted.
Authors: Paula Aldaz; Jaione Auzmendi-Iriarte; Maika Durántez; Irene Lasheras-Otero; Estefania Carrasco-Garcia; M Victoria Zelaya; Laura Bragado; Ana Olías-Arjona; Larraitz Egaña; Nicolás Samprón; Idoia Morilla; Marta Redondo-Muñoz; Mikel Rico; Massimo Squatrito; Marta Maria-Alonso; Joaquín Fernández-Irigoyen; Enrique Santamaria; Iñaki M Larráyoz; Claudia Wellbrock; Ander Matheu; Imanol Arozarena Journal: Cancers (Basel) Date: 2021-01-19 Impact factor: 6.639
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