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.

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


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

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Asbestos Case Beats Statute of Limitations

A federal judge has denied a pump manufacturer’s argument that an asbestos-related lung cancer case should be tossed because it wasn’t filed in time.

As asbestos litigation continues its steady decline and fewer lawsuits against companies for asbestos-related illnesses make it past the early stages of litigation, plaintiff Kathleen Conneen’s case on behalf of her deceased husband, Joseph Conneen, has cleared a significant hurdle.

U.S. District Judge Eduardo C. Robreno of the Eastern District of Pennsylvania denied defendant Goulds Pumps Inc.’s motion for summary judgment based on Pennsylvania’s two-year statute of limitations in asbestos cases, and under maritime law. Joseph Conneen worked in a shipyard.

The primary dispute centers on when Kathleen Conneen’s husband learned his exposure to asbestos could have been a factor in his diagnosis. According to Robreno’s opinion, Joseph Conneen, who filed suit in January 2015, was diagnosed with lung cancer in December of 2012.

Kathleen Conneen argued that her husband did not learn that asbestos exposure was a possible factor until February 2013, while Goulds countered that since Conneen’s husband worked around asbestos for 28 years and never smoked, he should have been more diligent in trying to identify the cause of his cancer.

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Source: Asbestos Case Beats Statute of Limitations

 


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Arizona High Court to Rule on Liability in Asbestos Take Home Exposure Case

The Arizona Supreme Court has agreed to consider whether employers can be held liable to somebody who contracted cancer from asbestos brought home on a parent’s work clothes.

The case stems from the 2014 death of Dr. Ernest Quiroz, whose 2013 negligence lawsuit contends he was exposed to asbestos on his father’s work clothes.

The facts as outlined in the appeal indicate he lived with his father from 1952 to 1966, during the time his father worked at Reynolds Metal Co. Dr. Quiroz lived in California until 1976 and in Michigan until his death in 2014. The suit alleges Dr. Quiroz contracted mesothelioma as a result of the exposure to his father’s work clothes.

The suit argues that Reynolds Metal Co. was legally obligated to avoid creating hazardous conditions that would injure people off its property.

Reynolds won a pretrial ruling by a trial judge, and the Court of Appeals upheld it.

The Court of Appeals said potential drawbacks of recognizing what’s called a duty of care in so-called “take-home exposure” cases outweigh potential benefits, partly by opening the door to liability claims involving an array of hazardous materials.

Source: Arizona High Court to Rule on Liability in Asbestos Take Home Exposure Case

 


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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


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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.

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


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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.

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Source: Lung-sparing surgery may boost mesothelioma survival


 

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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.

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


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Asbestos ban to be announced by federal government next week

The federal government plans to announce a comprehensive ban on asbestos in Canada next week, CBC News has learned.

The country currently allows imports of construction products and automotive parts that contain the toxic fibre, even though Canada no longer exports the material.

Asbestos is known to cause deadly cancers and lung diseases, and has already been banned in Europe, Australia and Japan. The World Health Organization recommends replacing asbestos with safer substitutes.

Canadian labour and public health groups have been calling for a comprehensive ban for years.

About 2,000 Canadians die of asbestos-related diseases every year — many of those deaths have been linked to asbestos exposure in the workplace.

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Source: Asbestos ban to be announced by federal government next week


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Canada should stop importing deadly asbestos, labour group says

The Canadian Labour Congress is calling for a ban on asbestos.

Exposure to asbestos — a fibrous mineral used in building and construction — is the leading cause of workplace-related death in Canada.

Canada stopped exporting asbestos in 2011, and its last asbestos mine closed in 2012. But Canada still imports asbestos for use in construction products and automotive parts.

According to the Canadian Labour Congress, the value of the imports has increased from $4.7 million in 2011 to $8.2 million in 2015.

Hassan Yussuff, president of the Canadian Labour Congress, told CBC’s The Early Edition the government needs to step up and ban the import of asbestos.

“We only stopped exporting it because the mine went bankrupt, not because this is good public policy.  We knew the evidence long before that asbestos is a carcinogen.”

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Source: Canada should stop importing deadly asbestos, labour group says


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Treatments to prolong life for mesothelioma patients closer

Researchers have uncovered a strange way that asbestos-related tumours grow, which could pave the way towards better treatments.

The scientists at Adelaide’s Flinders University have found that malignant mesothelioma tumours are able to transform into blood vessels, promoting their own growth.

Associate Professor Sonja Klebe said the behaviour was unusual.

“Instead of waiting for the outside of the tissue to grow blood vessels in, the tumour cells themselves branch out, growing blood vessels that reach out into surrounding tissues, tapping into the native vasculature,” she said.

Existing tumour treatments target blood vessels that grow into the cancer, and not the other way around.

“So I think a future approach would involve treating both of these types of vessels to more or less starve the tumour of blood supply,” Associate Professor Klebe said.

[Article continues at original source]

Source: Treatments to prolong life for mesothelioma patients closer


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