Systemic management of malignant meningiomas: A comparative survival and molecular marker analysis between Octreotide in combination with Everolimus and Sunitinib

Cardona, Andrés F.; Ruíz-Patiño, Alejandro; Zatarain-Barrón, Zyanya Lucía; Hakim, Fernando; Jiménez, Enrique; Mejía, Juan Armando; Ramón, Juan Fernando; Useche, Nicolás; Bermúdez, Sonia; Pineda, Diego; Cifuentes, Hernando; Rojas, Leonardo; Ricaurte, Luisa; Pino, Luis Eduardo; Balaña, Carmen; Arrieta, Óscar

doi:10.1371/journal.pone.0217340

Cited by 23 publications

(62 citation statements)

References 20 publications

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“…The standard systemic therapies, such as sunitinib and everolimus/octreotide, have been evaluated to control aggressively recurrent meningiomas, but their clinical efficiency is poor [ 14 , 15 , 16 ]. More recently, the Lutathera combining [ 177 Lu]Lu-DOTA-TATE with [ 68 Ga]Ga-DOTA-TATE or [ 68 Ga]Ga-DOTA-TOC DOTA-(D-Phe1, Tyr3)-octreotide is being evaluated in clinical trials for meningioma treatment [ 11 , 44 , 45 ].…”

Section: Resultsmentioning

confidence: 99%

“…The anti-SSTR2 ADC had no obvious off-target effects on body weight, overall survival, and major organs, which indicates that it is a safe targeted therapy for SSTR2-positive meningioma. The standard systemic therapies, such as sunitinib and everolimus/octreotide, have been evaluated to control aggressively recurrent meningiomas, but their clinical efficiency is poor [14][15][16]. More recently, the Lutathera combining [ 177 Lu]Lu-DOTA-TATE with [ 68 Ga]Ga-DOTA-TATE or [ 68 Ga]Ga-DOTA-TOC DOTA-(D-Phe1, Tyr3)-octreotide is being evaluated in clinical trials for meningioma treatment [11,44,45].…”

Section: Toxicity Evaluationmentioning

confidence: 99%

“…All these cultures were incubated at 37 °C and 5% CO2 in a humidified incubator (Caron, Marietta, OH, USA). The viable cell density (VCD) and viability were measured using a Countess II au- The standard systemic therapies, such as sunitinib and everolimus/octreotide, have been evaluated to control aggressively recurrent meningiomas, but their clinical efficiency is poor [14][15][16]. More recently, the Lutathera combining [ 177 Lu]Lu-DOTA-TATE with [ 68 Ga]Ga-DOTA-TATE or [ 68 Ga]Ga-DOTA-TOC DOTA-(D-Phe1, Tyr3)-octreotide is being evaluated in clinical trials for meningioma treatment [11,44,45].…”

Section: Cell Lines Seed Cultures and Mediamentioning

confidence: 99%

“…Clinicians have been using radio-labeled octreotide (a somatostatins analog), e.g., gallium-68 ( 68 Ga)-DOTATATE [ 7 , 11 ], as a brain scintigraphy tracer to delineate the extent of meningiomas and to pathologically define extra-axial lesions. In addition to diagnosis and detection [ 12 , 13 ], somatostatin analog, in combination with other systemic therapy, such as everolimus/octreotide, has demonstrated the ability to inhibit meningioma tumor growth [ 14 , 15 , 16 ], although further investigation is needed [ 8 , 17 , 18 ]. Despite these achievements, it is imperative to develop a targeted therapy to treat SSTR2-positive low- and high-grade meningiomas.…”

Section: Introductionmentioning

confidence: 99%

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Antibody–Drug Conjugate to Treat Meningiomas

Chen

et al. 2021

Pharmaceuticals

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Meningiomas are primary tumors of the central nervous system with high recurrence. It has been reported that somatostatin receptor 2 (SSTR2) is highly expressed in most meningiomas, but there is no effective targeted therapy approved to control meningiomas. This study aimed to develop and evaluate an anti-SSTR2 antibody–drug conjugate (ADC) to target and treat meningiomas. The meningioma targeting, circulation stability, toxicity, and anti-tumor efficacy of SSTR2 ADC were evaluated using cell lines and/or an intracranial xenograft mouse model. The flow cytometry analysis showed that the anti-SSTR2 mAb had a high binding rate of >98% to meningioma CH157-MN cells but a low binding rate of <5% to the normal arachnoidal AC07 cells. The In Vivo Imaging System (IVIS) imaging demonstrated that the Cy5.5-labeled ADC targeted and accumulated in meningioma xenograft but not in normal organs. The pharmacokinetics study and histological analysis confirmed the stability and minimal toxicity. In vitro anti-cancer cytotoxicity indicated a high potency of ADC with an IC50 value of <10 nM. In vivo anti-tumor efficacy showed that the anti-SSTR2 ADC with doses of 8 and 16 mg/kg body weight effectively inhibited tumor growth. This study demonstrated that the anti-SSTR2 ADC can target meningioma and reduce the tumor growth.

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Section: Resultsmentioning

confidence: 99%

Section: Toxicity Evaluationmentioning

confidence: 99%

Section: Cell Lines Seed Cultures and Mediamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antibody–Drug Conjugate to Treat Meningiomas

Chen

et al. 2021

Pharmaceuticals

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“…As an orally administered small tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), KIT and platelet-derived growth factor receptor, sunitinib has been demonstrated active in patients with recurrent malignant meningioma in a phase II trial where the 6month progression-free survival (PFS) rate in the cohort of anaplastic and atypical meningiomas was 42% and the expression of VEGFR2 in the tumor tissue was associated with favorable PFS (16). Moreover, sunitinib showed similar efficacy and safety in the systemic management of refractory meningiomas compared with octreotide/everolimus (17).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Identification of a Novel GNAS Mutation and 1p/22q Co-Deletion in a Patient With Multiple Recurrent Meningiomas Sensitive to Sunitinib

Hong

Shan

et al. 2021

Front. Oncol.

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BackgroundAlthough surgical resection can cure the majority of meningiomas, there are still approximately 20% of patients suffering from an aggressive course with recurrence or progression. In this study, we reported a novel GNAS mutation and 1p/22q co-deletion responding to sunitinib in a patient with multiple recurrent meningiomas.Case PresentationA 53-year-old woman with meningioma was hospitalized due to postoperative tumor progression for 3 weeks. WHO grade I meningioma was pathologically diagnosed after the first three surgeries, but the second recurrence occurred approximately 3 years following the third surgery. Next-generation sequencing was performed on the first two recurrent samples. GNAS mutations and 1p/22q co-deletion were both identified, and amplification at 17q and chromosome 19 was also found in the second recurrent sample, based on which WHO grade II/III meningioma was diagnosed. The lesion in the left cerebellopontine angle area enlarged after use of radiotherapy combined with temozolomide chemotherapy for 2 months. When sunitinib was added, the residual lesions began to lessen and continuously reduced.ConclusionThis typical case suggested that timely molecular diagnosis for refractory meningiomas contributed to guiding the molecular classification and clinicians to make more reasonable individualized therapeutic regimens, consequently benefiting the patients. This case report also highlighted the potential role of sunitinib in the treatment of refractory meningiomas.

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