A Phase II Study of Intermittent Sunitinib Malate as Second-Line Therapy in Progressive Malignant Pleural Mesothelioma

Nowak, Anna K.; Millward, Michael; Creaney, Jenette; Francis, Roslyn J.; Dick, Ian M.; Hasani, Arman; Schaaf, Agatha Van Der; Segal, Amanda; Musk, Arthur W.; Byrne, Michael

doi:10.1097/jto.0b013e31825f22ee

Cited by 86 publications

(52 citation statements)

References 43 publications

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“…Malignant mesothelioma is an uncommon cancer (2) with limited therapeutic options (8,(10)(11)(12) and poor clinical outcomes (4,5). Thus, we investigated the genomic landscape of this tumor by targeted NGS.…”

Section: Discussionmentioning

confidence: 99%

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Genomic Landscape of Malignant Mesotheliomas

Kato

Tomson²,

Buys³

et al. 2016

Molecular Cancer Therapeutics

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Understanding the genomic landscape of malignant mesothelioma may identify novel molecular drivers of this ultra-rare disease, which can lead to an expanded roster of targeted therapies and clinical trial options for patients with mesothelioma. We examined the molecular profiles of 42 patients with malignant mesothelioma (including pleural, peritoneal, and pericardial) that were referred by clinicians to be tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory using next-generation sequencing (NGS; 182 or 236 genes). Among 42 patients, there were 116 alterations, with 92 being distinct. The number of genomic alterations per patient ranged from 1 to 5 (median ¼ 3 [trend]; OR 5.8, P ¼ 0.01 [CDKN2A/B]). All 42 patients had a molecular abnormality that was potentially actionable (median ¼ three actionable alterations per patient; range, 1 to 5), and, in 40 patients (95.2%), a drug approved by the FDA was applicable. In conclusion, each individual with malignant mesothelioma harbored a unique set of genomic aberrations, suggesting that NGSbased profiling of patients will be needed if patients are to be optimally matched to cognate treatments. All 42 patients had at least one alteration that was, in theory, pharmacologically tractable. Mol Cancer Ther; 15(10); 2498-507. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

“…Molecular singletons as the norm are commonly reported in other cancers as well (44)(45)(46)(47)(48). Considering that effective therapies for mesothelioma are lacking (8)(9)(10)(11)(12), clinical trials for mesothelioma that incorporate molecular profiling for patient selection and appropriately customized therapy are warranted (49).…”

Section: Discussionmentioning

confidence: 99%

Genomic Landscape of Malignant Mesotheliomas

Kato

Tomson²,

Buys³

et al. 2016

Molecular Cancer Therapeutics

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“…Pazopanib was well tolerated and the primary endpoint PFS rate at 6 months was 47% [Garland et al 2011] [ClinicalTrials.gov identifier: NCT00459862]. Sunitinib, a similar multitargeted TKI, demonstrated variable results in patients with pretreated disease and has also not moved forward into further trials [Laurie et al 2011;Nowak et al 2012].…”

Section: Inducing Angiogenesismentioning

confidence: 99%

Malignant pleural mesothelioma: an update on diagnosis and treatment options

Kondola

Manners

Nowak

2016

Ther Adv Respir Dis

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Malignant pleural mesothelioma (MPM) represents a significant diagnostic and therapeutic challenge and is almost always a fatal disease. Imaging abnormalities are common, but have a limited role in distinguishing mesothelioma from metastatic pleural disease. Similarly, minimally invasive biomarkers have shown promise but also have limitations in the diagnosis of mesothelioma. In experienced centers, cytology and immunohistochemistry are now sufficient to diagnose the epithelioid subtype of mesothelioma, which can reduce the need for more invasive diagnostic investigations. Prognosis of MPM is modestly impacted by oncological treatments. Chemotherapy with cisplatin and pemetrexed is considered the standard of care, though the addition of bevacizumab to the platinum doublet may be the new standard of care. New targeted therapies have demonstrated some promise and are being addressed in clinical trials. This review focuses on the current data on the diagnostic and therapeutic issues of MPM.

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“…This was the reason to proceed with a larger randomized phase II trials testing cediranib in combination with pemetrexed and cisplatin. A second phase II study of sunitinib as second-line therapy reported modest activity in progressing patients, but was unable to identify any serum biomarkers of response in angiogenesis pathways [45]. A large randomized phase III study examined the oral antiangiogenic drug thalidomide in a switch maintenance setting.…”

Section: Vascular Targeted Drugsmentioning

confidence: 99%

Second line therapy in malignant pleural mesothelioma: A systematic review

et al. 2015

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a b s t r a c tAfter the implementation of standard first line chemotherapy with platinum and antifolates in pleural mesothelioma, patients are confronted with a need for second line treatment at relapse or progression. We conducted a systematic review of the literature for the activity, effectiveness and toxicity of second line treatment. The results are presented according to the class of drugs: chemotherapy and targeted or biological agent.

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A Phase II Study of Intermittent Sunitinib Malate as Second-Line Therapy in Progressive Malignant Pleural Mesothelioma

Abstract: Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.

Cited by 86 publications

References 43 publications

Genomic Landscape of Malignant Mesotheliomas

Genomic Landscape of Malignant Mesotheliomas

Malignant pleural mesothelioma: an update on diagnosis and treatment options

Second line therapy in malignant pleural mesothelioma: A systematic review

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