Randomized Phase Ii Trial Avareg (Ml25739) with Bevacizumab (Bev) or Fotemustine (Ftm) in Recurrent Gbm: Final Results from the Randomized Phase Ii Trial

Brandes, Aa; Finocchiaro, Gaetano; Zagonel, Vittorina; Fabi, Alessandra; Caserta, Claudia; Reni, Michele; Clavarezza, Matteo; Maiello, Evaristo; Cartenì, Giacomo; Rosti, Giovanni; Eoli, Marica; Lombardi, Giuseppe; Monteforte, Marta; Agati, R.; Eusebi, Vincenzo; Gallì, Anna; Doria, Simona; Franceschi, Enrico

doi:10.1093/annonc/mdu330.1

Cited by 8 publications

(5 citation statements)

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“…The 9-month os was 37.9% and 46.7% in the bevacizumab and fotemustine arms respectively. Median os was 7.3 months (95%ci: 5.8 to 9.2 months) in the bevacizumab arm and 8.7 months in the fotemustine arm 49 .…”

Section: Treatment With Antiangiogenicsmentioning

confidence: 98%

Nonsurgical Treatment of Recurrent Glioblastoma

2015

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Standard treatment for glioblastoma multiforme is surgery followed by radiotherapy and chemotherapy, generally with temozolomide. However, disease recurs in almost all patients. Diagnosis of progression is complex given the possibility of pseudoprogression.The Response Assessment in Neuro-Oncology criteria increase the sensitivity for detecting progression. Most patients will not be candidates for new surgery or re-irradiation, and anticancer drugs are the most common approach for second-line treatment, if the patient's condition allows. Antiangiogenics, inhibitors of the epidermal growth factor receptor, nitrosoureas, and re-treatment with temozolomide have been studied in the second line, but a standard therapy has not yet been established. This review considers currently available medical treatment options for patients with glioblastoma recurrence.

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Section: Treatment With Antiangiogenicsmentioning

confidence: 98%

Nonsurgical Treatment of Recurrent Glioblastoma

2015

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“…In the AVAREG trial [4], a numerical imbalance of baseline characteristics in favor of fotemustine in terms of worse PS (19 vs 9%), corticosteroids use (71 vs 62%) and tumor area (1024 vs 575 mm 2 ) was found, as well a longer time between diagnosis to MRI at screening (331 vs 462 days).…”

Section: Introductionmentioning

confidence: 99%

“…The AVAREG trial [4] randomized 91 patients (2:1) to receive bevacizumab or fotemustine, a third generation nitrosourea, largely used in Italy [13]. RANO criteria were adopted for the disease assessment, and also Macdonald's criteria were recorded.…”

Section: Introductionmentioning

confidence: 99%

“…In Europe, the EMA did not approve this agent despite the promising results in terms of response rate and progression-free survival provided by early Phase II studies without a calibration arm [1,2]. Therefore, new prospective randomized trials with bevacizumab in the recurrent setting have been conducted, and have been recently reported: the BELOB [3] and the AVAREG [4] trials.Both these trials adopted overall survival rates as primary end points, to avoid issues related to response assessment [5], and included a nitrosourea calibration arm, generating novel information in this setting.For many years response rate was considered the primary end point for Phase II studies in medical oncology. In neurooncology progression-free survival (PFS) and, in particular the incidence of patients free of progression at 6 months (PFS-6) have been considered the most appropriate end point for Phase II studies since the nineties [6], radiological responses being scarce (6-8%) [7,8], and there being a correlation between PFS and overall survival [9].…”

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confidence: 99%

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The role of bevacizumab in recurrent glioblastoma: new insights from randomized trials

Franceschi

Brandes

2015

CNS Oncol.

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The role of bevacizumab in the setting of recurrent glioblastoma (GBM) is still an argument of debate. In Europe, the EMA did not approve this agent despite the promising results in terms of response rate and progression-free survival provided by early Phase II studies without a calibration arm [1,2]. Therefore, new prospective randomized trials with bevacizumab in the recurrent setting have been conducted, and have been recently reported: the BELOB [3] and the AVAREG [4] trials.Both these trials adopted overall survival rates as primary end points, to avoid issues related to response assessment [5], and included a nitrosourea calibration arm, generating novel information in this setting.For many years response rate was considered the primary end point for Phase II studies in medical oncology. In neurooncology progression-free survival (PFS) and, in particular the incidence of patients free of progression at 6 months (PFS-6) have been considered the most appropriate end point for Phase II studies since the nineties [6], radiological responses being scarce (6-8%) [7,8], and there being a correlation between PFS and overall survival [9].Yet the action of bevacizumab on blood-brain barrier permeability directly affects the MRI evaluation made in these cases, thus potentially compromising the reliability of the assessment of the response rate and PFS. Therefore PFS-6 was no longer considered a sound end point [5].In the BELOB trial [3], a randomized Phase II study that enrolled 153 patients to receive bevacizumab alone or in combination with lomustine, or lomustine alone, Taal and Colleagues adopted the Response Assessment in Neuro-Oncology (RANO) criteria [10] for disease assessment, and reported that the radiological response following bevacizumab was correlated with survival (HR: 0.37; 95% CI: 0.23-0.58). These results are consistent with those reported in previous retrospective analyses in which imaging-based end points (response rate or PFS), obtained with bevacizumab were found to correlate with survival [11,12].Does this suggest that the best end point in Phase II studies should be re-reviewed?As yet, these findings are suggestive that neuroradiology still has a role in disease assessment for patients treated with bevacizumab, but further data are needed.

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Nitrosoureas in the Management of Malignant Gliomas

Brandes

Bartolotti

Tosoni

et al. 2016

Curr Neurol Neurosci Rep

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Nitrosoureas represent one of the most active classes of agents in the treatment of high-grade gliomas and glioblastoma. In clinical practice, the most commonly used compounds are lomustine (either alone or in combination with procarbazine and vincristine), carmustine, and fotemustine. Given their toxicity profile and subsequent to the introduction of temozolomide in clinical practice, most of these agents were moved to the recurrent setting. This review focuses on the role of the nitrosoureas currently used in clinical practice for the treatment of malignant gliomas.

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Randomized Phase Ii Trial Avareg (Ml25739) with Bevacizumab (Bev) or Fotemustine (Ftm) in Recurrent Gbm: Final Results from the Randomized Phase Ii Trial

Cited by 8 publications

References 0 publications

Nonsurgical Treatment of Recurrent Glioblastoma

Nonsurgical Treatment of Recurrent Glioblastoma

The role of bevacizumab in recurrent glioblastoma: new insights from randomized trials

Nitrosoureas in the Management of Malignant Gliomas

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