Clinical Safety and Activity of Pembrolizumab in Patients With Malignant Pleural Mesothelioma

BACKGROUND  Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort.

METHODS  Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries. Patients received pembrolizumab (10 mg/kg every 2 weeks) for up to 2 years or until confirmed progression or unacceptable toxicity….

FINDINGS  As of June 20, 2016, 25 patients received pembrolizumab. 16 (64%) patients reported a treatment-related adverse event; the most common adverse event were fatigue (six [24%]), nausea (six [24%]), and arthralgia (five [20%])….

INTERPRETATION  Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1-positive malignant pleural mesothelioma. Response durability and efficacy in this patient population warrants further investigation.

[Read full article at original source]

Source: Clinical Safety and Activity of Pembrolizumab in Patients With Malignant Pleural Mesothelioma


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma

Purpose: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with few therapeutic options. The tumor–stromal interface is important in MPM, but this is lost in cell lines, the main model used for preclinical studies. We sought to characterize MPM patient-derived xenografts (PDX) to determine their suitability as preclinical models and whether tumors that engraft reflect a more aggressive biological phenotype.

Experimental Design: Fresh tumors were harvested from extrapleural pneumonectomy, decortication, or biopsy samples of 50 MPM patients and implanted subcutaneously into immunodeficient mice and serially passaged for up to five generations. We correlated selected mesothelioma biomarkers between PDX and patient tumors, and PDX establishment with the clinical pathologic features of the patients, including their survival. DNA of nine PDXs was profiled using the OncoScan FFPE Express platform. Ten PDXs were treated with cisplatin and pemetrexed.

Results: A PDX was formed in 20 of 50 (40%) tumors implanted. Histologically, PDX models closely resembled the parent tumor. PDX models formed despite preoperative chemotherapy and radiotherapy. In multivariable analysis, patients whose tumors formed a PDX had significantly poorer survival when the model was adjusted for preoperative treatment (HR, 2.46; 95% confidence interval, 1.1–5.52; P = 0.028). Among 10 models treated with cisplatin, seven demonstrated growth inhibition. Genomic abnormalities seen in nine PDX models were similar to that previously reported.

Conclusions: Patients whose tumors form PDX models have poorer clinical outcomes. MPM PDX tumors closely resemble the genotype and phenotype of parent tumors, making them valuable models for preclinical studies.

Source: Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study

Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.

[Article continues at original source]

Source: Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Lung-sparing surgery may boost mesothelioma survival

Surgery that preserves the lung, when combined with other therapies, appears to extend the lives of people with a subtype of the rare and deadly cancer mesothelioma, a new study suggests.

Tracking 73 patients with advanced malignant pleural mesothelioma—which affects the lungs’ protective lining in the chest cavity—researchers found that those treated with lung-sparing had an average survival of nearly three years. A subset of those patients survived longer than seven years.

Mesothelioma patients treated with chemotherapy alone, which is standard care, live an average of 12 to 18 months, the researchers said.

Study participants received lung-sparing surgeries and another treatment called photodynamic therapy that uses light to kill cancer cells. Ninety-two percent of the group also received chemotherapy.

The study volunteers achieved far longer survival times, said study author Dr. Joseph Friedberg.

“When you take the [entire] lung out, it’s a significant compromise in quality of life,” said Friedberg. He’s director of the University of Maryland Medical Center’s Mesothelioma and Thoracic Oncology Treatment and Research Center in Baltimore.

“For all intents and purposes, this [lung-sparing surgical approach] is the largest palliative operation known to man, since chances of curing mesothelioma are vanishingly small,” said Friedberg. He completed the research while at his previous post at the University of Pennsylvania.

“Plus, most of these patients are elderly, so preserving quality of life was really the goal,” he added.

[Article continues at original source]

Source: Lung-sparing surgery may boost mesothelioma survival


 

 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Asbestos-related cancer won’t be overcome anytime soon, doctors say

New methods are giving doctors a better handle on diagnosing and treating asbestos-related cancers, but no cures are on the horizon.

“I think it would be overly optimistic to say it’s going to be cured. I mean we can always dream,” said oncologist Dr. Christopher Lee, an expert on mesothelioma.

Paul Demers, a senior scientist in prevention at the Occupational Cancer Research Centre in Toronto, said one of the difficulties in diagnosing mesothelioma is the long latency period — the period between exposure and the development of symptoms — which can sometimes be up to 40 years.

When asbestos fibres are inhaled or ingested, they become trapped in the pleural lining of the lungs. Over time, thousands of tiny fibres cause scarring in the tissue.

New equipment like the CyTOF instrument allows doctors to detect asbestos earlier and with more precision, which could facilitate more effective treatments for asbestos victims.

[Article continues at original source]

Source: Asbestos-related cancer won’t be overcome anytime soon, doctors say


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Malignant Mesothelioma in a Motor Vehicle Mechanic

Case reports remain an important source of data in the debate over the carcinogenic effect of asbestos-containing automotive friction products. This report documents a case of pleural mesothelioma accompanied by asbestos bodies in the lung tissue of a career auto mechanic with no other known sources of exposure. Previously unreported historical and contemporary exposure data are also discussed in the context of providing additional support for the proposition that work with asbestos-containing automotive products presents a risk of significant exposure. While there remains a body of negative epidemiology that fails to find an increased risk of disease among auto workers, those data must be approached with caution. Many of those studies have drawn technical criticisms, which are beyond the scope of this report, but they remain a key part of the legal defense mounted by defendant-companies who are involved in asbestos-related litigation. This ongoing debate provides the context for the continued relevance of case reports such as this one, as well as the presentation of new and previously unpublished exposure data.

Source: Malignant Mesothelioma in a Motor Vehicle Mechanic


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Myxoid variant epithelioid pleural mesothelioma defines a favourable prognosis group: an analysis of 191 patients with pleural malignant mesothelioma

Malignant pleural mesothelioma shows marked cytoarchitectural diversity. The aim of the study was to evaluate how morphological phenotype impacted upon overall survival. 191 cases of malignant pleural mesothelioma with available follow-up were identified, examined and classified according to histological types. The epithelioid mesotheliomas were further subdivided according to morphological subtypes: myxoid, microcystic, tubulopapillary, solid epithelioid, micropapillary and pleomorphic; biphasic mesotheliomas were divided into epithelioid component dominant and sarcomatoid component dominant; pure sarcomatoid mesotheliomas were divided into not otherwise specified, leiomyoid, desmoplastic and heterologous. All cases were confirmed by two experienced observers. Myxoid variant malignant pleural epithelioid mesothelioma was observed to have a favourable overall survival compared with pleomorphic form (p=0.00008). Pleomorphic phenotype had the worst overall survival. Morphological phenotype is an important histological factor that should be included in pathology reports to convey potential favourable prognostic subgroups of patients with mesothelioma.

Source: Myxoid variant epithelioid pleural mesothelioma defines a favourable prognosis group: an analysis of 191 patients with pleural malignant mesothelioma


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Residual fibre lung burden among patients with pleural mesothelioma who have been occupationally exposed to asbestos

Objectives  To evaluate the lungs asbestos fibres concentration in participants with malignant pleural mesothelioma (MPM) who have been occupationally exposed.

Methods  The lung samples were obtained from pleuropneumonectomies or autopsies of 271 male MPMs. The lung samples were examined through scanning electron microscopy. Retrospective assessment was used to assess for asbestos exposure. This study includes 248 MPMs with an occupational exposure defined as either ‘definite’ or ‘probable’ or ‘possible’.

Results  The participants had finished working in asbestos exposure conditions more than 20?years ago (on average 26.1±11.0?years). The fibre burden resulted with a geometric mean equal to 2.0 (95% CI 1.6 to 2.4) million fibres per gram of dry lung tissue. The burden was higher among participants employed in asbestos textiles industry and in shipyards with insulation material, if compared with construction workers or non-asbestos textile workers or participants working in chemicals or as auto mechanics. 91.3% of MPMs had a detectable amount of amphibole fibres. A strong lung clearance capability was evident among workers exposed to chrysotile fibres. Owing to that, the 1997 Helsinki Criteria for occupational exposure were reached in <35% of cases among participant working in construction, in metallurgical industry, in chemical or textile industry and among those performing brake repair activities.

Conclusions  The MPM cases are now occurring in Italy in participants who ceased occupational asbestos exposure decades before the analysis. A large majority still shows a residual content of amphibole fibres, but given the lung clearance capability, attribution to occupational exposure cannot rely only on fibres detection.

Source: Residual fibre lung burden among patients with pleural mesothelioma who have been occupationally exposed to asbestos


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Arginine Deprivation for Malignant Pleural Mesothelioma

Arginine deprivation is a novel anticancer strategy in argininosuccinate synthetase 1 (ASS1)–negative tumors. In a multicenter, phase II trial, immunohistochemistry identified 68 patients with ASS1 deficiency among 201 patients with malignant pleural mesothelioma (MPM). The ASS1-deficient patients were randomized in a 2:1 ratio to either best supportive care (BSC) or BSC plus intramuscular ADI-PEG20, a pegylated arginine deiminase that causes arginine deprivation, at 36.8 mg/m2 weekly (in 4-week cycles) for up to 6 months. Of the ADI-PEG20 recipients, 23% received six treatment cycles.

During a median follow-up of 38 months, no participants had partial or complete response. However, stable disease at 4 months (using modified Response Evaluation Criteria in Solid Tumors [RECIST]) was significantly more common with ADI-PEG20 than with BSC alone (52% vs. 22%). ADI-PEG20 also outperformed BSC alone significantly in median progression-free survival (PFS; 3.2 vs. 2.0 months; hazard ratio, 0.56) and nonsignificantly in median overall survival (11.5 vs. 11.1 months) and life expectancy (15.7 vs. 12.1 months). The most common ADI-PEG20 toxicities were grade 1–2 nonfebrile neutropenia, gastrointestinal events, injection-site reactions, and fatigue; grade 3 events, in 25% of ADI-PEG20 recipients, were anaphylaxis and serum sickness. The two treatment groups had similar quality of life (whether patient- or observer-reported).

[Article continues at original source]

Source: Arginine Deprivation for Malignant Pleural Mesothelioma


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Malignant mesothelioma of the pleura with desmoplastic histology: a case series and literature review

Abstract

Background

Desmoplastic malignant pleural mesothelioma (DMM) is rare histological subtype of diffuse malignant pleural mesothelioma (MPM), accounting for 5–10 % of cases. It has a poor prognosis, with direct invasion of the chest wall or lungs and distant metastases. Its pathological characteristics include dense collagen fibers in a storiform pattern. Its pretreatment pathological diagnosis is difficult, with fibrous pleuritis and reactive mesothelial hyperplasia as potential differential diagnoses.

Case presentation

We retrospectively reviewed the medical charts of patients with MPM from 1996 to 2012. Among 60 patients with MPM, four patients with the desmoplastic subtype were identified and their clinical characteristics, including asbestos exposure, treatment, and prognosis, were reviewed. All of the patients with DMM were men, with a median age of 69 years (range: 63–74 years). All four patients had been exposed to asbestos. The definitive diagnosis was made histologically and the International Mesothelioma Interest Group classification was advanced (III/IV: 2/3) in all four patients. Three patients were treated with chemotherapy (two with cisplatin/pemetrexed and one with cisplatin/gemcitabine) and one patient underwent surgery. The median survival time in the patients with DMM was 3.8 months (range: 0.9–11.5 months), compared with 10.5 months in patients with other subtypes of MPM in our institution.

Conclusions

DMM continues to have a poor prognosis. It is important to recognize this variant and distinguish it from pleural plaques, non-specific reactive pleural fibrosis, pleurisy, and other lung diseases.

Source: Malignant mesothelioma of the pleura with desmoplastic histology: a case series and literature review


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

Asbestos-Mesothelioma Case Evaluation Form
Free.  Confidential.  No Obligation.

Law Offices of Thomas J. Lamb, P.A.
1908 Eastwood Road, Suite 225
Wilmington, NC 28403
Tel: (800) 426-9535
Email@LambLawOffice.com
Disclaimer and Copyright