Parp-Inhibitors show promise in mesothelioma treatment

At this year’s American Association for Cancer Research, investigators from the United Kingdom announced the positive results of a mesothelioma clinical trial testing a relatively new class of targeted drugs: the PARP inhibitors.

The study Niraparib Efficacy in Patients With Unresectable Mesothelioma (NERO) enrolled 88 patients randomized into two groups showed that those treated with niraparib extended the median progression-free survival by 1.5 months compared to the arm of patients who only received symptom management care.

Eligible patients had already undergone standard chemotherapy treatment for mesothelioma with success, but they relapsed with the cancer coming back or growing.

Currently, there are no proven therapies for mesothelioma beyond initial treatment and after recurrence. Data on the efficacy of chemotherapy are limited, and immunotherapy retreatment has been only a recent addition to the doctors’ treatment arsenal.

What are PARP inhibitors?

Simply put, PARP inhibitors are drugs that prevent the enzyme known as poly ADP ribose polymerase (PARP) from doing its job of repairing damaged DNA in cells. If not repaired, damaged cells, including cancer cells, die. Conversely, if repaired, even if the repair is erroneous, the cells go on to survive and replicate which can be problematic with cancerous cells. Typically, patients who responded to chemotherapy previously are more likely to see a benefit from this class of drugs. While this study did not require patients enrolled to have a somatic BAP1 deletion, other studies looking into this agent often do. Somatic mutations are those not passed down to offspring and are instead acquired in the cells over time. BAP1 is a tumor suppressor gene, therefore its deletion is understood as consequential in mesothelioma.

Clinical trials employing PARP inhibitors currently available in the United States

While this study took place in the United Kingdom, in the U.S. clinical studies utilizing PARP inhibitors have been available to mesothelioma patients who fit certain eligibility criteria. Currently, one of those studies is still open and enrolling.

Olaparib in Patients with HRD Malignant Mesothelioma is available at the University of Chicago Medicine to patients with the loss of BAP1 and/or a germline (passed down from parents) or somatic (acquired over lifetime) mutation that disrupts protein function in at least one of the patient’s genes.

Could there be another mesothelioma cell type beyond epithelioid, sarcomatoid, and biphasic?

In recent years, mesothelioma histology has become more important than ever, as researchers find that certain treatments are more effective against different cell types. The epitheliod subtype of mesothelioma is by far the most common and is considered the least aggressive of the three types. The sarcomatoid subtype is less common but most aggressive. When a tumor contains both types of cells, it is known as biphasic.

As far as treatment goes, epitheliod mesothelioma tends to respond to chemotherapy better than the sarcomatoid subtype, while benefits of immunotherapy are more pronounced in patients with the more aggressive sarcomatoid subtype.

But now, researchers believe to have identified mesothelioma cells that are neither sarcomatoid nor epitheliod. In the preprint article “Comprehensive multi-site profiling of the malignant pleural mesothelioma micro-environment identifies candidate molecular determinants of histopathologic type,” by Raphael Bueno, MD, et al., the authors suggest that a third category of cells exist in the tumor microenvironment of mesothelioma and are most prevalent in tumors of patients with biphasic disease. Those cells have been named “uncommitted” because the idea is that at some point they might take on an epitheliod or sarcomatoid appearance.

As the researchers examined tumor samples, they noticed that in predominantly epitheliod, and in predominantly sarcomatoid mesotheliomas, such uncommitted cells were few, but in biphasic mesothelioma they were substantial.

Significance of histology (tumor cell type) for mesothelioma patients

The cellular type of the mesothelioma tumor helps doctors determine the prognosis and best treatment for a patient. For example, it is currently known that survival varies depending on the cell type. Patients with epitheliod mesothelioma have the best prognosis, and those with sarcomatoid the worst. The biphasic patients tend to fall in between depending on the proportion of epitheliod vs sarcomatoid cells in their tumors. Moreover, tumor histology helps doctors identify the best treatment for a patient. Sarcomatoid and biphasic tumors have shown the greatest benefit when treated with immunotherapy, and the least benefit when treated with chemotherapy. As mesothelioma research continues to advance, the tumor microenvironment is seen as far more important than individual cells in the proliferation of this cancer.

Because mesothelioma prognosis currently relies so heavily on histology, this discovery adds another layer of nuance to an already complex disease. In addition to understanding the significance and purpose of these uncommitted cells, another question for researchers to untangle in the future will be to understand whether these uncommitted cells ultimately become committed, and whether they commit to the epitheliod or sarcomatoid type and why.

New episode of Meet the Mesothelioma Experts About Financial Compensation for Mesothelioma

Last week, the Mesothelioma Applied Research Foundation released a new episode of its Meet the Mesothelioma Experts: Legal Edition series discussing financial compensation issues for mesothelioma patients. Featured guest of the program was Joseph Belluck, partner with the Belluck & Fox firm, who was interviewed by the organization’s board of directors’ member, Cheryl Bruner. Mr. Belluck answered a number of questions of interest to those who have just had a mesothelioma diagnosis and their families.

Acting with Urgency

One of the take-home messages is that while a mesothelioma diagnosis requires medical urgency and treatment, so does the legal process. This is due to a number of issues, the statute of limitations being one, but not the only one. As Mr. Belluck states in this program, it is important to file a lawsuit as soon as realistically possible in order to get a place in line, even if later adjustments are necessary. An experienced law firm will know enough information about a case very quickly and will be able to proceed with expedience.

“Usually, right after contact, we file the case, we start working on the bankruptcy trust claims and also starting to work on the lawsuit, which we do in tandem. Typically, the first settlements will come in about 45 – 60 days and the whole case will be completed within 12 months,” said Mr. Belluck in the program.

Mr. Belluck adds that whether a patient chooses to hire his firm or another firm, he still encourages them to make sure to do so quickly for the reasons outlined above.

Watch the video:

00:00 Introduction
1:11 Why Belluck & Fox chooses to sponsor the Meso Foundation and how their mission resonates
6:15 How Belluck & Fox works within the meso community
7:47 Next steps in the legal process after diagnosis
11:05 Litigation timeline after choosing a law firm
14:01 How much time and effort is anticipated to dedicate to litigation
16:14 Options for taking legal action
21:58 Timeline of settlement funds
28:05 How much of a settlement does a patient/family receive
35:37 Advice for future clients in deciding legal action

Compensation Programs for Mesothelioma Patients and their Families

There are several main compensation programs that are typically available to mesothelioma patients. They include simple programs like health insurance, private disability insurance, social security disability benefits, and workers compensation if the person is still employed. Additionally, veterans’ benefits are available for people who served in the military and have a service connection to asbestos exposure. Mesothelioma bankruptcy trusts are another avenue to pursue for compensation. There are about 40-50 individual funds that have been set up by companies that made asbestos products and went into bankruptcy. As part of their bankruptcy reorganization, they set up a fund for their product. And the last option available is to file a lawsuit individually, not a class action, against the companies that made asbestos products that the patient was exposed to.

Mr. Belluck and his law firm offer free consultations by submitting a quick form on the firm’s website at www.belluckfox.com.

Mesothelioma Treatment News: Delivering therapies directly into the pleural space

In a new article published in the medical journal The Lancet (Leveraging the pleural space for anticancer therapies in pleural mesothelioma by Blythe at al., 2024), authors make an argument for renewed focus toward therapies that can be delivered directly into the intrapleural space.

The benefit of such therapies is that by targeting the tumor directly, doctors are able to use higher doses of medication for increased likelihood of success while limiting toxicity to the patient.

Pleural mesothelioma is a cancer of the lining that surrounds the lung, which is called the pleura. So far, most attention has been devoted toward finding systemic treatments that work – a feat that has proven to be quite challenging. Systemic treatments are treatments such as chemotherapy or immunotherapy, which are administered through a vein, that travel throughout the entire body to kill the cancer cells wherever they may be. These treatments are currently the standard of care, but many patients’ tumors still don’t respond to them well. Because most patients’ cancer is quite advanced at diagnosis, this approach is often the only option anyway.

However, some patients receive a very early diagnosis either incidentally, meaning they underwent a surgical procedure for a different issue when mesothelioma was found; or because they presented with fluid buildup in the pleural space (called a pleural effusion) that prompted further testing. Recent staging studies suggest that this population of patients is significantly larger than previously thought and might include anywhere between 15% to 40% of diagnoses. For such patients, benefits of systemic therapies are unclear because studies that led to the FDA approval of chemotherapy and immunotherapy predominantly included unresectable (non-surgical candidates) stage 3 and 4 patients. Typically, early-stage patients are either offered surgery, or watchful waiting. But in the past year, this approach has been further complicated by a somewhat controversial surgical study called MARS 2 which showed limited benefits of surgery in the management of mesothelioma. Therefore, the expectation is that the number of early-stage patients who receive no immediate treatment will increase.

For this reason, the authors suggest that development of studies to test the effectiveness of localized intrapleural treatment is important and feasible and can be performed during the wait period between diagnosis and standard treatment, called window of opportunity.

In its early stages, mesothelioma’s only symptom might be a pleural effusion, either symptomatic or not. If symptomatic, once the effusion is drained, the patient feels better. But as long as mesothelioma is present on the pleura, it is rare for the fluid to stop building up. Currently, there are two ways to manage this problem:

With a procedure called pleurodesis. The purpose of the procedure is to close the space in the pleura where fluid accumulates. This procedure makes the pleural space mostly inaccessible.
By inserting a drain catheter into the pleural space to drain the fluid as it builds up, thus leaving the pleural space accessible.

Critically, administering intrapleural therapy will require access to the pleura, so the initial course of action for palliation of the pleural fluid will need to be reviewed and will require consensus among providers. It is important to note that a previous pleurodesis might not necessarily be a disqualifying factor as long as pleural pockets of air/fluid are still present.

This article is a summary of a research study and does not constitute medical advice.

Thanksgiving: Giving Thanks to all Those in the Mesothelioma Community

Holidays can be challenging when you or a loved one is dealing with a serious medical issue.

Thanksgiving is a day steeped in traditions; A time for turkey, football, family, and all the reasons to give thanks, we share these rituals with family and friends yearly. If this is the first one that you or your loved one are celebrating with a diagnosis of malignant mesothelioma chances are this one is different.

With the new perspective that comes with dealing with a rare cancer, and facing the unknown that is ahead, giving thanks takes on a new meaning. In addition to your usual support systems, this is a time to lean on the community that surrounds and tirelessly advocates for those afflicted with this mostly preventable cancer.

The mesothelioma community is an active group of family members, researchers, advocates, and caregivers all committed to supporting and advocating for patients and their families. From support groups, political activism, and advocates in the medical and legal community, the work moves forward. This small community continues to support and hopefully improve the lives of the victims and their families.

The mesothelioma community has made extensive accomplishments that slowly, and hopefully, will lead to a cure. We are grateful for the teams of researchers who have dedicated their lives to finding treatments for this complex cancer. The team consists of many people that work in behind-the-scenes labs that are required to complete this extensive work. It is not always successful, but they continue tirelessly, as each new day lays the stepping stones leading to a cure. Although the work is necessary and important, it often goes unnoticed. Without their contributions, there can be no new innovative therapies. We applaud and give thanks for their continued work.

Advocates within the mesothelioma community continue to work on behalf of all victims and their families. They have been working for decades now, to place into law, a nationwide ban on asbestos. The goal has never been closer. This could not be made possible without patients and family members who have made this their lives work advocating for a total ban on the leading cause of Malignant Mesothelioma, asbestos. Knowing the devastation that asbestos causes, they continue on so others may not have to suffer the losses they have. We applaud and give thanks for their continued work.

Caregivers of patients with Malignant Mesothelioma are constantly coordinating, researching, and helping the patients on a daily basis. These caregivers consist mostly of unpaid family members who sacrificed their time and energy, often at the cost of their own health. We applaud and give thanks for their continued work.

On this Thanksgiving, we want to take this time to give thanks to all those in the mesothelioma community that continue to support patients and their loved ones.

Happy Thanksgiving!

Resources Available;

www.curemeso.org

www.asbestosdiseaseawareness.org

Category: Mesothelioma