Current evidence and challenges of systematic therapies for adult recurrent glioblastoma: Results from clinical trials

Chen, Wenlin; Liu, Delin; Liu, Penghao; Kong, Ziren; Wang, Yaning; Wang, Yu; Ma, Wenbin

doi:10.21147/j.issn.1000-9604.2021.03.12

Cited by 6 publications

(6 citation statements)

References 99 publications

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“… [ 20 ] 2021, Chen et al Review rGBM NA NA No pooled data Studies showed that BEV was effective in prolonging PFS and alleviating edema but had no effect on prolonging OS. [ 94 ] 2021, Detti et al Retrospective study rHGG 92 (100%) BEV + chemotherapy vs. BEV monotherapy Median OS : BEV vs. BEV + other chemotherapy: 9.4 months (7.7–13.4) vs. 8.9 months (95% CI 7.2–11.7) No significant difference [ 95 ] 2021, Zheng et al Review rGBM NA NA No pooled data LOM was the only chemotherapy drug that improved the efficacy of BEV in rGBM. [ 17 ] 2021, Yamaguchi et al Retrospective study rGBM 73 (58.9%) Cytoreductive surgery + BEV vs. BEV monotherapy vs. BSC Median OS (since the first recurrence) : Cytoreductive surgery + BEV vs. BEV vs. BSC: 16.3 months; 7.4 months; 4.6 months (p = 0.0008) BEV plus cytoreductive surgery improved OS compared with BEV monotherapy.…”

Section: Resultsmentioning

confidence: 99%

Use of Bevacizumab in recurrent glioblastoma: a scoping review and evidence map

Zhou

Huang

et al. 2023

BMC Cancer

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Background Glioblastoma (GBM) is the most malignant primary tumor in the brain, with poor prognosis and limited effective therapies. Although Bevacizumab (BEV) has shown promise in extending progression-free survival (PFS) treating GBM, there is no evidence for its ability to prolong overall survival (OS). Given the uncertainty surrounding BEV treatment strategies, we aimed to provide an evidence map associated with BEV therapy for recurrent GBM (rGBM). Methods PubMed, Embase, and the Cochrane Library were searched for the period from January 1, 1970, to March 1, 2022, for studies reporting the prognoses of patients with rGBM receiving BEV. The primary endpoints were overall survival (OS) and quality of life (QoL). The secondary endpoints were PFS, steroid use reduction, and risk of adverse effects. A scoping review and an evidence map were conducted to explore the optimal BEV treatment (including combination regimen, dosage, and window of opportunity). Results Patients with rGBM could gain benefits in PFS, palliative, and cognitive advantages from BEV treatment, although the OS benefits could not be verified with high-quality evidence. Furthermore, BEV combined therapy (especially with lomustine and radiotherapy) showed higher efficacy than BEV monotherapy in the survival of patients with rGBM. Specific molecular alterations (IDH mutation status) and clinical features (large tumor burden and double-positive sign) could predict better responses to BEV administration. A low dosage of BEV showed equal efficacy to the recommended dose, but the optimal opportunity window for BEV administration remains unclear. Conclusions Although OS benefits from BEV-containing regimens could not be verified in this scoping review, the PFS benefits and side effects control supported BEV application in rGBM. Combining BEV with novel treatments like tumor-treating field (TTF) and administration at first recurrence may optimize the therapeutic efficacy. rGBM with a low apparent diffusion coefficient (ADCL), large tumor burden, or IDH mutation is more likely to benefit from BEV treatment. High-quality studies are warranted to explore the combination modality and identify BEV-response subpopulations to maximize benefits.

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Section: Resultsmentioning

confidence: 99%

Use of Bevacizumab in recurrent glioblastoma: a scoping review and evidence map

Zhou

Huang

et al. 2023

BMC Cancer

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“…The PACIFIC studies have established the therapeutic status of immune-consolidation therapy in patients with GBM after simultaneous RT and chemotherapy (43)(44)(45). However, the selection of PD-1/PD-L1 inhibitors and the timing of RT and chemotherapy are still under exploration.…”

Section: Discussionmentioning

confidence: 99%

“…PACIFIC study and a series of comparable investigations revealed that PD-1/PD-L1 monoclonal antibody has advantages in disease control, prolonging survival time, and improving patient quality of life in first-line at stage-III NSCLC suffers ( 43 ). Devaruzumab, an inhibitor of PD-1/PD-L1 binding ( 44 , 45 ), is already approved by the FDA US as first-line standard therapy after simultaneous RT and chemotherapy for patients with stage III NSCLC. The latest 4-year survival data of the PACIFIC study indicated median PFS of stage III NSCLC suffers treated by simultaneous RT and chemotherapy combined with devaruzumab was 17.2 months, while that of the placebo group was only 5.6 months (MD, 0.51), reducing disease advancement or mortality with 49%.…”

Section: Discussionmentioning

confidence: 99%

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Effects of postoperative radiotherapy and docetaxel and PD-1 inhibitors on the survival and safety of glioblastoma patients: a systematic review and meta-analysis

Yang¹,

Wang²,

Liu³

et al. 2022

Ann Transl Med

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Background: The present standard treatment rarely allows the complete removal of glioblastoma (GBM).So postoperative treatments are provided to prevent or delay tumor recurrence. The overall survival (OS) rate and safety of postoperative chemotherapy alone, or combined with radiotherapy (RT), or programmed cell death-1 (PD-1) inhibitor in GBM is still unclear. The present goal was to explore postoperative treatment's effect on the survival and safety of patients with GBM.Methods: We searched the mainstream online databases for clinical studies of RT and chemotherapy and PD-1 inhibitors in the treatment of GBM published up to May 2020. The patients in the experimental group accepted an anti-PD-1 drug alone and RT + chemotherapy, whereas the controlled patients were treated with docetaxel alone. The literature qualities were assessed using Cochrane Risk of Bias 2.0, and studies were assigned. The meta-analysis was conducted by RevMan 5.4 software.Results: A total of 927 articles were identified through the online database search. The articles unable to meet the inclusion criteria were excluded leaving 6 studies for inclusion in the study. Compared with docetaxel-based chemotherapy for GBM, combined RT chemotherapy and PD-1 inhibitor therapy had better OS [mean difference (MD), −1.75; 95% confidence interval (CI): −2.99 to −0.51; P=0.006] and progression-free survival (PFS) and a lower incidence of adverse reactions (MD, −7.03; 95% CI: −7.64 to −6.42; P<0.00001) above grade III.Conclusions: Postoperative combination of RT and chemotherapy and PD-1 inhibitors had some advantages over docetaxel in terms of effectiveness. More clinical trials are needed to confirm effectiveness.

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“… 4–6 Therefore, there is an unmet clinical need to distinguish between PsP and true tumor progression during the early course of treatment to aid in the decision to continue surveillance or initiate other treatment options such as anti-angiogenic therapy, targeted therapy, or immunotherapy. 7 …”

mentioning

confidence: 99%

Magnetic resonance spectroscopy outperforms perfusion in distinguishing between pseudoprogression and disease progression in patients with glioblastoma

El-Abtah

Talati

et al. 2022

Neuro-Oncology Advances

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Background There is a need to establish biomarkers that distinguish between pseudoprogression (PsP) and true tumor progression in patients with glioblastoma (GBM) treated with chemoradiation. Methods We analyzed magnetic resonance spectroscopic imaging (MRSI) and dynamic susceptibility contrast (DSC) MR perfusion data in patients with GBM with PsP or disease progression after chemoradiation. MRSI metabolites of interest included intratumoral choline (Cho), myo-inositol (mI), glutamate+glutamine (Glx), lactate (Lac) and creatine on the contralateral hemisphere (c-Cr). Student T-tests and area under the ROC curve analyses were used to detect group differences in metabolic ratios and their ability to predict clinical status, respectively. Results 28 subjects (63±9 years, 19 men) were evaluated. Subjects with true progression (N=20) had decreased enhancing region mI/c-Cr (P=0.011), a marker for more aggressive tumors, compared to those with PsP, which predicted tumor progression (AUC: 0.84 [0.76, 0.92]). Those with true progression had elevated Lac/Glx (P=0.0009), a proxy of the Warburg effect, compared to those with PsP which predicted tumor progression (AUC: 0.84 [0.75, 0.92]). Cho/c-Cr did not distinguish between PsP and true tumor progression. Despite rCBV (AUC: 0.70 [0.60, 0.80]) and rCBF (AUC: 0.75 [0.65, 0.84]) being individually predictive of tumor response, they added no additional predictive value when combined with MRSI metabolic markers. Conclusions Incorporating enhancing lesion MRSI measures of mI/c-Cr and Lac/Glx into brain tumor imaging protocols can distinguish between PsP and true progression and inform patient management decisions.

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Current evidence and challenges of systematic therapies for adult recurrent glioblastoma: Results from clinical trials

Cited by 6 publications

References 99 publications

Use of Bevacizumab in recurrent glioblastoma: a scoping review and evidence map

Use of Bevacizumab in recurrent glioblastoma: a scoping review and evidence map

Effects of postoperative radiotherapy and docetaxel and PD-1 inhibitors on the survival and safety of glioblastoma patients: a systematic review and meta-analysis

Magnetic resonance spectroscopy outperforms perfusion in distinguishing between pseudoprogression and disease progression in patients with glioblastoma

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