The current landscape of systemic therapy for recurrent glioblastoma: A systematic review of randomized-controlled trials

Fazzari, Francesco; Rose, Foster; Pauls, Mehrnoosh; Guay, Evelyne; Ibrahim, Mohammed; Basulaiman, Bassam; Tu, Megan M.; Hutton, Brian; Nicholas, Garth; Ng, Terry L.

doi:10.1016/j.critrevonc.2021.103540

Cited by 12 publications

(13 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All of our data are consistent with the findings of recent studies [ 9 , 11 ]. They show that none of the traditionally used regimens is unequivocally better than the others for the second-line treatment of GB.…”

Section: Discussionsupporting

confidence: 94%

“…Median OS2 was 17.7 months for the TMZ group and 11.6 months for the nitrosourea group, and median PFS2 was 8.1 months for the TMZ group and 5.8 months for the nitrosourea group. Other studies have shown that the benefit of TMZ rechallenge may be restricted to patients with tumors displaying MGMT promoter methylation [ 3 , 11 , 46 , 47 ]. It would be interesting to compare TMZ rechallenge with other regimens in prospective randomized trials in patients with a long TFR and/or with MGMT-promoter methylated GB to determine the optimal second-line treatment for these patients.…”

Section: Discussionmentioning

confidence: 99%

“…They show that none of the traditionally used regimens is unequivocally better than the others for the second-line treatment of GB. In recent years, a multitude of novel drugs, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, have shown promising signs of efficacy against rGB, but the reported responses were observed in a highly selected and very limited patient population [ 9 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…There is universal agreement about the first-line treatment for primary GB, but the best way to manage recurrent GB (rGB) is less clear, given that none of the treatments used for recurrences has ever been shown to be more beneficial than the others [ 3 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The management of rGB is based on expert guidelines, such as those of the European Society for Medical Oncology (ESMO) [ 16 ], the European Association of Neuro-Oncology (EANO) [ 3 ], the National Comprehensive Cancer Network (NCCN, (accessed on 1 February 2022)) and “Association des Neuro-Oncologues d’Expression Française” (ANOCEF, (accessed on 1 January 2018)).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Clavreul

Autier

Lemée

et al. 2022

Cancers

View full text Add to dashboard Cite

Safe maximal resection followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) is universally accepted as the first-line treatment for glioblastoma (GB), but no standard of care has yet been defined for managing recurrent GB (rGB). We used the French GB biobank (FGB) to evaluate the second-line options currently used, with a view to defining the optimal approach and future directions in GB research. We retrospectively analyzed data for 338 patients with de novo isocitrate dehydrogenase (IDH)-wildtype GB recurring after TMZ chemoradiotherapy. Cox proportional hazards models and Kaplan–Meier analyses were used to investigate survival outcomes. Median overall survival after first surgery (OS1) was 19.8 months (95% CI: 18.5–22.0) and median OS after first progression (OS2) was 9.9 months (95% CI: 8.8–10.8). Two second-line options were noted for rGB patients in the FGB: supportive care and treatments, with systemic treatment being the treatment most frequently used. The supportive care option was independently associated with a shorter OS2 (p < 0.001). None of the systemic treatment regimens was unequivocally better than the others for rGB patients. An analysis of survival outcomes based on time to first recurrence (TFR) after chemoradiotherapy indicated that survival was best for patients with a long TFR (≥18 months; median OS1: 44.3 months (95% CI: 41.7–56.4) and median OS2: 13.0 months (95% CI: 11.2–17.7), but that such patients constituted only a small proportion of the total patient population (13.0%). This better survival appeared to be more strongly associated with response to first-line treatment than with response to second-line treatment, indicating that the recurring tumors were more aggressive and/or resistant than the initial tumors in these patients. In the face of high rates of treatment failure for GB, the establishment of well-designed large cohorts of primary and rGB samples, with the help of biobanks, such as the FGB, taking into account the TFR and survival outcomes of GB patients, is urgently required for solid comparative biological analyses to drive the discovery of novel prognostic and/or therapeutic clinical markers for GB.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Clavreul

Autier

Lemée

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…4 Since, no highly effective treatment has been found for disease recurrence, the choice of the best second-line therapy remains an open issue. 5 To date, the most employed medical treatments at recurrence consist of nitrosourea-based schedules and / or antiangiogenic therapy. Lomustine, a nitrosourea alkylating agent, has been used as control in several phase 2 and 3 trials, [6][7][8][9][10][11][12][13] with a low objective response rate (around 10%), almost exclusively limited to patients with O6-methylguanine DNA methyltransferase promoter (MGMTp) methylation.…”

mentioning

confidence: 99%

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

et al. 2022

View full text Add to dashboard Cite

Purpose: In the phase 2 REGOMA trial, regorafenib improved overall survival, as compared with lomustine, in glioblastoma (GBM) patients at rst progression after chemoradiation. 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. The aim of this study was to assess the e cacy and tolerability of a lower intensity regorafenib regimen.Patients and Methods: Regorafenib daily dose was gradually increased from 80 to 160 mg across the rst 2 cycles. Progression-free survival (PFS) and overall survival (OS) were de ned as time from regorafenib initiation and disease progression or death. Results: Sixty-six GBM patients were included. Median age was 60.0 years. Median PFS and OS following regorafenib were 2.7 and 7.1 months, respectively. Best RANO response to regorafenib were partial response (PR) in 10 (15.1%), stable disease in 17 (25.8%), and progressive disease in 39 (59.1%) patients. Forty-six (69.7%) patients presented adverse events of any grade, and 21 (31.8%) grade 3-4 toxicity. In a multivariable analysis, higher age and absence of MGMTp methylation were signi cantly associated with poorer disease control after regorafenib.Conclusions: Our study is the largest observational real-life study on the use of regorafenib. Our lower intensity regimen proved as effective as the standard 160 mg daily schedule (mPFS and mOS being 2.7 vs 2.0 months and 7.1 vs 7.4 months in our study vs REGOMA, respectively). Moreover, we observed a higher rate of PRs as compared with REGOMA (15.0% versus 3.0%). Background Glioblastoma (GBM) is the most common primary brain tumour of the adult. 1 To date, the standard treatment of newly diagnosed GBM is maximal surgical resection followed by chemoradiation using temozolomide (TMZ). 2,3 However, disease progression occurs in almost all patients after rst line treatment, and median overall survival (OS) is of the order of 20 months. 4 Since, no highly effective treatment has been found for disease recurrence, the choice of the best second-line therapy remains an open issue. 5 To date, the most employed medical treatments at recurrence consist of nitrosourea-based schedules and / or antiangiogenic therapy. Lomustine, a nitrosourea alkylating agent, has been used as control in several phase 2 and 3 trials, [6][7][8][9][10][11][12][13] with a low objective response rate (around 10%), almost exclusively limited to patients with O6-methylguanine DNA methyltransferase promoter (MGMTp) methylation. 8,10,12 Bevacizumab is a recombinant humanised antibody that blocks angiogenesis by inhibiting the vascular endothelial growth factor receptor A (VEGF-A). As GBM is a highly vascularised tumour with increased endothelial proliferation and VEGFR expression, 14 bevacizumab has been investigated in several trials in both newly diagnosed and recurrent GBM. 15 Overall, it has been shown to increase progression-free survival (PFS), but not OS. 10 Regorafenib is an oral inhibitor of several kinases involve...

show abstract

Current and Future Drugs for Brain Tumors Treatment

Bruno,

Pellerino,

Marchesani

et al. 2024

Advanced Imaging and Therapy in Neuro-Oncology

View full text Add to dashboard Cite

The current landscape of systemic therapy for recurrent glioblastoma: A systematic review of randomized-controlled trials

Cited by 12 publications

References 91 publications

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

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

Current and Future Drugs for Brain Tumors Treatment

Contact Info

Product

Resources

About