The epithelioid BAP1‐negative and p16‐positive phenotype predicts prolonged survival in pleural mesothelioma

Chou, Angela; Toon, Christopher W.; Clarkson, Adele; Sheen, Amy; Sioson, Loretta; Gill, Anthony J.

doi:10.1111/his.13392

Cited by 21 publications

(16 citation statements)

References 21 publications

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“…27 In addition, we observed a doubling of the median survival (6.5 versus 3.5 mo) and a three-fold increase in survival at 12 months (30% versus 10%), compared with historical controls for sarcomatoid mesothelioma. 1,26 Although response assessment in mesothelioma is challenging, and reported infrequently in trials for the nonepithelioid disease, the 93.5% disease control rate is encouraging and consistent with the earlier dose-escalation study findings. 12 Collectively, these data benchmarked the design of the ATOMIC-meso (ADI-PEG 20 Targeting Of Malignancy Induces Cytotoxicity-Mesothelioma) study, which transitioned from phase 2 to phase 3 earlier this year after successful recruitment of 176 patients with nonepithelioid mesothelioma; a further 210 patients are being enrolled to report on the primary end point of OS (ClinicalTrials.gov identifier NCT02709512).…”

Section: Discussionsupporting

confidence: 72%

“…23,24 Moreover, twice as many patients were alive at 15 months with biphasic compared with the epithelioid disease (40% versus 20%), indicating that the latter subgroup is at the aggressive end of the spectrum and concurring with the poor-prognosis epithelioid disease defined by nuclear grading and p16 loss on multivariate analysis. 25,26 Notably, the 8.2 month median OS for nonepithelioid disease compares favorably with the recent SWOG S0905 trial reporting a median OS of 6.3 months for PemCis plus placebo or 6.5 months for PemCis plus the vascular endothelial growth factor receptor antagonist, cediranib (n ¼ 23; nonepithelioid). 27 In addition, we observed a doubling of the median survival (6.5 versus 3.5 mo) and a three-fold increase in survival at 12 months (30% versus 10%), compared with historical controls for sarcomatoid mesothelioma.…”

Section: Discussionmentioning

confidence: 62%

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Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1–Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms

Szlosarek

Phillips

Pavlyk

et al. 2020

JTO Clinical and Research Reports

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Introduction: Pegargiminase (ADI-PEG 20; ADI) degrades arginine and potentiates pemetrexed (Pem) cytotoxicity in argininosuccinate synthetase 1 (ASS1)-deficient malignant pleural mesothelioma (MPM). We conducted a phase 1 dose-expansion study at the recommended phase 2 dose of ADI-PEG 20 with Pem and cisplatin (ADIPemCis), to further evaluate arginine-lowering therapy in ASS1-deficient MPM and explore the mechanisms of resistance. Methods: A total of 32 patients with ASS1-deficient MPM (11 epithelioid; 10 biphasic;11 sarcomatoid) who were chemonaive received weekly intramuscular pegargiminase (36 mg/m 2) with Pem (500 mg/m 2) and cisplatin (75 mg/ m 2) intravenously, every 3 weeks (six cycles maximum). Maintenance pegargiminase was permitted until disease progression or withdrawal. Safety, pharmacodynamics, immunogenicity, and efficacy were determined. Biopsies were performed in progressing patients to explore the mechanisms of resistance to pegargiminase. Results: The treatment was well tolerated. Most adverse events were of grade 1/2, whereas four nonhematologic grade 3/4 adverse events related to pegargiminase were reversible. Plasma arginine decreased whereas citrulline increased; this was maintained by 18 weeks of ADIPemCis *Corresponding author. Disclosure: Dr. Szlosarek has received support from the Higher Education Funding Council for England and research support from the Polaris Group. Drs. Bomalaski, Johnson, and Feng are paid employees of Polaris Pharmaceuticals. The remaining authors declare no conflict of interest.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 62%

Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1–Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms

Szlosarek

Phillips

Pavlyk

et al. 2020

JTO Clinical and Research Reports

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“…According to our results, BAP1 was relatively insensitive marker (low sensitivity of 44.6%) in detecting malignant mesothelioma. Our results matched those of Nasu et al, 2015;; Righi et al, 2016;Hida et al, 2017;Yoshimura et al, 2017;Chou et al, 2018;Kinoshita et al, 2018(b), andYoshimura et al, 2019, who all reported low BAP1 sensitivity, ranging from 50-65%.…”

Section: Discussionsupporting

confidence: 91%

Comparative study of BAP1 and CD147 expression in the diagnosis of malignant mesothelioma

Heabah

Eid

2020

International Journal of Cancer and Biomedical Research

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It is with great pleasure that I write this editorial to welcome you to the IJCBR. This journal provides a platform for publication of original and reviews research articles, short communications, letter to editor, thesis abstract, conference report, and case studies. These types of publication are directed at the interface of the fields of cancer and biomedical research.The IJCBR relies on a distinguished expert of the Advisory and Editorial Board Members from the top international league covering in depth the related topics. They timely review all manuscripts and maintain highest standards of quality and scientific methodology and ethical concepts. Meanwhile, we take all possible means to keep the time of the publication process as short as possible.I take this chance to welcome your contributions to the IJCBR and have every expectation that it will soon become one of the most respected journals in both the fields of cancer and biomedical research.

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“…The type (domestic, environmental or occupational), intensity and period of asbestos exposure, as well as genetic predisposition might impact on clinical characteristics of MPM patients and their prognosis [40]. Further analyses need to explore if this is rather a reflection of indolent biology or also a consequence of treatment efficacy [41][42].…”

Section: Discussionmentioning

confidence: 99%

Real-life treatment practice for malignant pleural mesothelioma in Belgium

Rosskamp¹,

Macq²,

Nackaerts

et al. 2018

Lung Cancer

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Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer, for which treatment is often limited to palliative combination chemotherapy. Multimodality-therapy, including radical surgery, is largely restricted to clinical trials, leaving its benefit currently unclear.This study aimed to get a comprehensive view on real-world MPM treatment at the Belgian population level, to assess survival and to identify prognostic factors. Materials and MethodsThe study period covered the incidence years 2004-2012 (N=1,453). Starting from the Belgian Cancer Registry, additional information regarding patient characteristics, diagnosis and treatment was retrieved from multiple data sources.Adjusted cox proportional-hazard regression models using time-dependent covariates were performed to assess survival in relation to treatment patterns and centre volume. ResultsSixty-nine percent of patients underwent tumour-directed treatment, mostly cisplatinpemetrexed chemotherapy. Radical surgery was mainly performed in younger patients with epithelioid subtype.Centre volume, surgery and chemotherapy showed a positive relation with survival in univariable analyses, but only chemotherapy remained significantly relevant in multivariable analyses. Younger patients, females, and epithelioid subtypes also independently had a better survival. ConclusionThis large population-based study provides insights in MPM treatment practice in Belgium.Centre volume and surgery being related to survival in univariable analyses, only chemotherapy remained prognostic after adjustment.

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The epithelioid BAP1‐negative and p16‐positive phenotype predicts prolonged survival in pleural mesothelioma

Abstract: In conclusion, p16 IHC is an independent prognostic biomarker in pleural mesothelioma. When used in combination with BAP1 IHC and morphological subtyping, patients with exceptionally prolonged survival can potentially be identified.

Cited by 21 publications

References 21 publications

Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1–Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms

Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1–Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms

Comparative study of BAP1 and CD147 expression in the diagnosis of malignant mesothelioma

Real-life treatment practice for malignant pleural mesothelioma in Belgium

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