ASCO Reading Room | Treatment Update for Malignant Pleural Mesothelioma | MedPage Today – Medpage Today

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In this exclusive MedPage Today interview, James Stevenson, MD, vice chairman of the Department of Hematology and Medical Oncology at Cleveland Clinic’s Taussig Cancer Institute, analyzes a recent review published in the Journal of Clinical Oncology by Anne S. Tsao, MD, MBA, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues about the many therapy options for malignant pleural mesothelioma, which usher in a “new era” for the disease.
Following is a transcript of his remarks:
I’m Dr. James Stevenson. I am a medical oncologist at Taussig Cancer Center in Cleveland Clinic. This month I want to review a publication from the Journal of Clinical Oncology from earlier this year, relating to therapeutic advances in the treatment of malignant pleural mesothelioma. This was published by Dr. Anne Tsao and colleagues.
This was a great recap of where we are in the treatment of pleural mesothelioma, which is a rare malignancy. But the number of cases in the United States has remained pretty constant despite asbestos use being essentially eliminated from the workplace. So we do still see mesothelioma and there’s still plenty of unmet needs in the treatment of this disease.
Part of the reason for this is just the nature of mesothelioma, that it involves poor diagnosis and typically the pleural is diffusely involved, so essentially these patients present with advanced disease, sometimes with more distant metastases, and local therapies have always been problematic.
The authors start with a review of the genomics of mesothelioma, which while the genomics have been pretty well elucidated through things like The Cancer Genome Atlas and other investigators such that we do know there are a number of relatively common genomic alterations in mesothelioma such as BAP1 and F1.
Despite knowledge of these alterations, they haven’t really proven to be druggable targets yet … But they are key in advancing our understanding of mesothelioma.
Another focus on treatment is where we are with surgery for mesothelioma at this point. Surgery has definitely played a decreasing role in the treatment of pleural mesothelioma, especially over the past decade — I think with the understanding that surgery for these patients is not truly with curative intent, as the goal of surgeries are macroscopic complete resections, and essentially are R01 resections, and that any surgery has to be employed with multimodality therapy, especially systemic therapy as a component.
And whether surgery truly offers a survival advantage versus other treatment modalities in mesothelioma is unknown. So fewer and fewer patients really are being offered surgery, such as extended pleurectomy, which is the most common procedure these days. Extrapleural pneumonectomy has really fallen out of favor in this country, and it’s very rarely performed.
So the surgery question is still probably best reserved for clinical trials. But outside of surgery we have had advances in other modalities, such as radiotherapy, such that pleural intensity-modulated radiotherapy, or pleural IMRT, can sometimes be employed by centers that have experience with this modality after surgery, or even in the primary therapy of patients with mesothelioma when incorporated with systemic chemotherapy.
I do anticipate that we’ll see further advances in radiotherapy modalities in mesothelioma. But I think the biggest excitement has been advances in systemic therapy. Pemetrexed and carboplatin have been a backbone of systemic chemotherapy in mesothelioma for almost the past 20 years. And thankfully we recently had an advance in immunotherapy for mesothelioma. The CheckMate 743 trial, which investigated nivolumab and ipilimumab combination therapy versus pemetrexed platinum chemotherapy, proved to be a positive trial, and that immunotherapy improved survival in patients with mesothelioma significantly. And it led to the approval of these agents here in the U.S.
Interestingly when the results are broken down by histology, there seems to be a clear advantage to the immunotherapy, especially in the sarcomatoid patients, whereas in the epithelioid patients the benefit was not as great.
So this seemed to be histology-driven outcomes here with the combination of immunotherapy in pleural mesothelioma. A lot of this was hypothesis generating for future trials, because there really was not otherwise a biomarker that helped us to decide on immunotherapy since CheckMate 743 was reported and these agents were approved. For instance, PD-L1 was not essentially predicted, so we can’t really use that to help select the immunotherapy to patients.
So pemetrexed platinum and nivolumab and ipilimumab are both excellent frontline options for patients. This can be chosen based on histology or even patient preference. So I think this helps our conversations with patients with mesothelioma to be much more inclusive so we can present these options to them and have the patients be involved in the decision.
And they’re not mutually exclusive, because immunotherapy can be used in the second-line setting after frontline pemetrexed-platinum, and vice versa. So we’ve at least really nicely expanded the systemic therapy options for these patients.
I think when we talk about future options, there’s a lot of excitement about chemoimmunotherapy based on some data with pemetrexed platinum and durvalumab. This is being looked at in a larger randomized trial right now, and there are other chemoimmunotherapy trials going on internationally. So perhaps that will be a step that will provide a clear winner in terms of what we should choose as frontline therapy.
Of course, all those studies are occurring and the results will be anxiously awaited in the not-too-distant future. So that’s exciting with chemoimmunotherapy therapy.
Also along the lines of immunotherapy is the use of CAR T-cells. There are multiple trials going on with CAR T-cell therapy. Most of those are being directed at the mesothelin protein, which is commonly over-expressed in mesothelioma, especially the epithelioid subtype. So certainly lots of interest there.
And in the U.K. there’s an interesting trial looking at biomarker-driven therapy with some genomic alterations, using things like PARP inhibitors. So targeted therapies are still of interest, even though there’s not a clear driver in mesothelioma.
So thankfully, even though this is a rare disease, there still is lots of interest in clinical investigations as translational investigations in mesothelioma internationally. So I predict we’ll see future advances in this disease in the not-too-distant timeframe.
Read the review here.
Read a related interview about it with NCI researcher Raffit Hassan, MD, here.
Primary Source
Journal of Clinical Oncology
Source Reference: Tsao AS, et al “New era for malignant pleural mesothelioma: Updates on therapeutic options” J Clin Oncol 2022: 40: 681-692.
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