Bevacizumab for Newly Diagnosed Malignant Pleural Mesothelioma

Adding bevacizumab to cisplatin and pemetrexed improves survival, but at a cost of higher toxicity.

Malignant pleural mesothelioma (MPM) is a challenging disease with few treatment options. In chemo-naive patients, pemetrexed plus a platinum agent remains the standard of care. To determine the potential benefit of adding bevacizumab to this regimen, French investigators conducted a randomized, controlled, open-label, phase III trial in which 448 patients with chemotherapy-naive, unresectable MPM received pemetrexed and cisplatin (PC) or pemetrexed and cisplatin plus bevacizumab (PCB) for 6 cycles; bevacizumab was continued as maintenance therapy in the PCB group….

Comment

This is the first randomized study to demonstrate efficacy of a triplet regimen and an anti-angiogenic agent for MPM patients. However, the associated toxicities require close monitoring of patients and limitations in patient eligibility. Moreover, this trial was strict in age eligibility (<76 years), and 97% of patients had performance-status 0–1. In addition, although it is common in the US (despite lack of randomized data) to give maintenance pemetrexed after 4–6 cycles of platinum-pemetrexed, this was not done in the current trial. Thus, it is unknown whether this triplet regimen with bevacizumab would provide a similar survival benefit compared with platinum-pemetrexed plus maintenance pemetrexed. Additional front-line anti-angiogenic trials are under way to assess other combination regimens, including pemetrexed and cisplatin plus cediranib (NCT01064648) and pemetrexed and cisplatin plus nintedanib (NCT01907100).

 

Source: Bevacizumab for Newly Diagnosed Malignant Pleural Mesothelioma

Wisconsin appeals court reinstates asbestos lawsuit against Pabst, Miller

A Wisconsin appeals court reinstated portions of a woman’s lawsuit Tuesday that alleges asbestos exposure at two of Milwaukee’s signature brewing companies played a role in her steamfitter husband’s death.

Sandra Brezonick’s lawsuit alleges her husband, John Brezonick, contracted mesothelioma after being exposed to asbestos at a number of Milwaukee-area industrial sites between 1996 and 2000. The lawsuit includes nearly a dozen defendants, including Pabst Brewing Company and Miller Brewing Company.

A judge last year dismissed her claims against Pabst, Miller, Sprinkmann Sons Corporation and Wisconsin Electric Power Company. She said a state law that prohibits lawsuits over injuries resulting from work to improve property shields them because John Brezonick’s work amounted to such improvements. The 1st District Court of Appeals reversed that decision, finding that the companies failed to prove his work amounted to improvements rather than repairs.

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Source: Wisconsin appeals court reinstates asbestos lawsuit against Pabst, Miller

 


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America’s ‘Third Wave’ Of Asbestos Disease Upends Lives

Everything seemed to be going smoothly for 39-year-old Kris Penny, who pulled fiber-optic cables for a living. Then he got a cancer called mesothelioma that’s almost always tied to asbestos exposure.

Until the morning of Sept. 25, 2014, life was treating Kris Penny well. His flooring company had just secured its first big contract.

But that morning, Penny, of Clermont, Fla., was feeling lethargic. He pulled into a McDonald’s for a cup of orange juice. Seconds after he drank it he doubled over in pain. “It felt like someone stabbed me in the stomach with a machete,” he said. A co-worker drove him to the emergency room.

When he awoke in the hospital, his wife, Lori McNamara, was beside him, crying. “I go, ‘What’s the matter? I’m still here,’ ” Penny said. The surgeon who’d opened up his abdomen had found it full of cancer — type to be determined. The doctor “pretty much told me to get my affairs in order, right there on the spot.”

The pathology results came in four days later. Penny learned that he had peritoneal mesothelioma — a rare cancer of the lining of the abdomen almost always tied to asbestos exposure. He concluded, after consulting with a lawyer, that he’d inhaled microscopic asbestos fibers about a decade earlier while installing fiber-optic cable underground. He sued telecommunications giant AT&T.

[Article continues at original source]

Source: America’s ‘Third Wave’ Of Asbestos Disease Upends Lives

 


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Determinants of Survival in Malignant Pleural Mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) Study of 14,228 Patients

Introduction

Left untreated, malignant pleural mesothelioma (MPM) is associated with uniformly poor prognosis. Better survival has been reported with surgery-based multimodality therapy, but to date, no trial has demonstrated survival benefit of surgery over other therapies. We evaluated whether cancer-directed surgery influenced survival independently from other predictors in a large population-based dataset.

Conclusions

Despite developments in surgical and radiation techniques, the prognosis for MPM patients has not improved over the past 4 decades. Cancer-directed surgery is independently associated with better survival, suggesting that multimodal surgery-based therapy can benefit these patients. Further research in adjuvant treatment is necessary to improve prognosis in this challenging disease.

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Source: Determinants of Survival in Malignant Pleural Mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) Study of 14,228 Patients

 


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Vaccine Promising for Multiple Cancer Indications in Phase 2 Trials

 

Sellas Life Sciences announced top-line data from the Phase 2 clinical study of its WT1 cancer vaccine in patients with malignant pleural mesothelioma (MPM).

The Phase 2 double-blind, randomized study compared WT-1 analog peptides vaccine in combination with Montanide-adjuvant plus granulocyte-macrophage colony-stimulating factor (GM-CSF) vs. Montanide-adjuvant plus GM-CSF in patients with MPM who had previously completed combined modality therapy. The study planned to enroll 39 patients in each arm, however, in May 2015, the trial’s independent Data Monitoring Committee requested discontinuation of the control arm due to futility while continuing the WT1 cancer vaccine arm. This change led to an earlier unblinding than planned, with total enrollment reaching 40 patients, 19 in the WT1 vaccine arm and 21 in the control arm.

[Article continues at original source]

Source: Vaccine Promising for Multiple Cancer Indications in Phase 2 Trials


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Celanese Corp. Socked With $14 Million Asbestos Wrongful Death Verdict

Posted by David Siegel on Oct 8, 2015

Spartanburg — A South Carolina state court jury slammed Texas-based materials company Celanese Corp. with a $14 million verdict on Thursday in a lawsuit brought by the family of a maintenance worker who died of cancer after being exposed to asbestos at a polyester fiber plant in the 1970’s.

The family of Dennis Seay, who died of mesothelioma in 2014 at the age of 70, was awarded $12 million in compensatory damages and $2 million in punitive damages following a 13-day trial. A second defendant in the case, gasket seller John Crane Inc., was cleared of all liability by the unanimous jury, according to a Courtroom View Network webcast of the proceedings.

Seay worked in a Celanese plant between 1971 and 1979 while an employee of Daniel Construction Co., which Celanese hired to perform maintenance and repair work. His lawsuit, filed in 2013, claimed Celanese and John Crane were aware of the dangers that asbestos insulation and asbestos-containing gaskets posed to workers but failed to give Seay adequate warnings of the risks.

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Source: Celanese Corp. Socked With $14 Million Asbestos Wrongful Death Verdict


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Bevacizumab in Malignant Pleural Mesothelioma

Panelists: Mary Jo Fidler, MD, Rush; Roy S. Herbst, MD, PhD, Yale ; Geoffrey R. Oxnard, MD, Harvard; Naiyer Rizvi, MD, Columbia; Mark A. Socinski, MD,
Published Online: Monday, October 5, 2015

Transcript:

Mark A. Socinski, MD: So in keeping with the same theme, we saw another antibody that’s been a part of our practice, bevacizumab, for years in nonsquamous non-small cell lung cancer, a very interesting trial from the French, the Mesothelioma trial, in which there was a clear survival advantage. Mary Jo, do you want to walk us through that?

Mary Jo Fidler, MD: It was a randomized trial of standard chemotherapy for mesothelioma with cisplatin and pemetrexed and the randomization was to add bevacizumab. And the study met its survival endpoint with a median survival reaching over the one year mark. I consider it a positive trial and I would use bevacizumab in this setting. I find it interesting for a couple of reasons. One is its movement in the disease that hasn’t had a lot of progress in several years.

Mark A. Socinski, MD: Well, much like squamous, right?

Roy S. Herbst, MD, PhD: Yes.

Mary Jo Fidler, MD: And a second thing, most of the non-small cell lung cancer data with bevacizumab, if it’s helping, it seems to be helping when you add it to a taxane backbone. Maybe there’s some antigenic synergism with the taxanes, but the data not including the taxane has been less impressive with pemetrexed in the European AVAIL trial. So bevacizumab reached its endpoint and it may be that the angiogenic pathway is much more important in mesothelioma.

Mark A. Socinski, MD: Is this an advance, Naiyer, in your opinion?

Naiyer Rizvi, MD: Absolutely! Mesothelioma is such a tough disease to treat, and I think that having a phase III trial that met its survival endpoint is very real and I think it changes practice.

[Article continues at original source]

Source: Bevacizumab in Malignant Pleural Mesothelioma


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Florida Supreme Court Revives $6.6M Asbestos Award Against Union Carbide

The Florida Supreme Court reinstated a $6.6 million award Thursday against Union Carbide Corp. in an asbestos case that attracted high-powered amicus briefs and hinged on what attorneys saw as either a pro-consumer or pro-business test.

The court opted for a products liability test that asked whether a product performed as safely as a reasonable consumer would expect.

The U.S. Chamber of Commerce, Pharmaceutical Research and Manufacturers of America and others argued for a strong public policy goal of limiting the duty of upstream manufacturers and suppliers to warn end users, Frank Cruz-Alvarez of Shook, Hardy & Bacon in Miami wrote in an amicus brief.

The Florida Consumer Action Network and the Florida Justice Association, representing plaintiffs lawyers, argued in support of the Miami-Dade Circuit Court verdict.

The Supreme Court majority chose to rely on the second restatement of torts by the American Law Institute in 1965 rather than the third restatement issued in 1997 that sets a higher burden for consumers bringing products liability cases.

Source: Florida Supreme Court Revives $6.6M Asbestos Award Against Union Carbide | Daily Business Review

 


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Commentary: Firefighters and teachers bear outsize burden of asbestos deaths

Asbestos does not discriminate.

It doesn’t matter who you are – young or old, strong or frail, rich or poor, factory worker or CEO – if you inhale or ingest even one microscopic asbestos fiber, you’re at increased risk of developing a deadly disease whose symptoms may not show up for decades.

But of the estimated 12,000 to 15,000 Americans who die of asbestos-related diseases each year, some groups do bear a disproportionate burden. The death rate is highest for workers in industries in which asbestos is or was extensively used, such as construction, shipbuilding, chemicals and railroads. But while each asbestos death is tragic, the tragedy feels most horrifying and unfair when it strikes those who were exposed through their unselfish service to society. Among those more likely than the average American to die from asbestos exposure are two such groups – one that willingly put themselves in harm’s way, another that may have never known they were at risk: firefighters and teachers.

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Abstract A36: Novel therapeutic approaches for human malignant mesothelioma

Human malignant mesothelioma (MM) is an aggressive and highly lethal cancer that has been linked to asbestos and erionite exposure. MM causes about 3,200 deaths per year in the US and more than 100,000 deaths per year worldwide. We previously found that high-mobility group box-1 protein (HMGB1), a prototypic damage-associated molecular pattern (DAMP), plays a critical role in the early events of HM malignant transformation and MM development. More recently we showed that MM cells are “addicted” to HMGB1 that supports the malignant phenotype by promoting proliferation and invasiveness of MM cells. We demonstrated that MM growth is inhibited by targeting HMGB1 using HMGB1 neutralizing antibody or BoxA, a HMGB1 antagonist. Ethyl pyruvate (EP) is the ethyl ester of pyruvic acid, known to suppress oxygen radical formation and HMGB1 secretion. Here we show that EP impaired motility, survival and proliferation of MM cells in vitro. Both BoxA and EP inhibited the activity of the pro-inflammatory transcription factor NF-kappaB, as well as reduced HMGB1 serum levels and the growth of MM xenografts in SCID mice. Taken together, our results provide a preclinical proof-of-principle that inhibition of HMGB1 activity using either HMGB1 antibody, BoxA or EP offers novel therapeutic approaches for MM treatment.

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