Promising Treatment Option for Unresectable Pleural Mesothelioma

IO Learning invited Bela Kis, MD, PhD, to discuss his 2020 Society of Interventional Radiology (SIR) Abstract of the Year, "Transarterial Chemoperfusion Treatment of Unresectable Pleural Mesothelioma: Interim Results of a Phase 2 Prospective Study.”¹ 

Can you share some background for the study?

Advanced malignant pleural mesothelioma (MPM) is associated with asbestos exposure and was considered a very rare disease until 50 years ago. The median latency between asbestos exposure and disease onset is 44.6 years, with the peak incidence projected to occur in 2020 and beyond. There are 2400 new cases each year in the United States, and the disease has an extremely poor prognosis, with a median survival time of <12 months. Surgical resection for stage I and II MPM is the only curative option; unfortunately, approximately 90% of patients present at a late stage and are considered unresectable at diagnosis. The current treatment options for unresectable MPM include chemotherapy and radiation therapy, which are largely ineffective.

In 2013, Vogl et al² presented a retrospective study on nonselective transarterial chemoperfusion for MPM, which involved direct injection of chemotherapy into the supplying artery of the tumor to achieve much higher chemotherapy concentration in the tumor compared with intravenous (IV) administration. They published excellent results, with approximately 14.2 month survival and about 80% disease control rate. The disadvantage of this treatment is that it is more invasive than traditional IV chemotherapy. Based on the promising results of this retrospective study, we designed an open-label, single-arm, phase 2 prospective study that included patients who had progressive disease following at least one line of chemotherapy.

Both the Vogl study and the present study utilized cisplatin (a DNA crosslinker) and gemcitabine (a nucleoside analogue). However, the Vogl study utilized mitomycin (another DNA crosslinker), which we opted to substitute with methotrexate (an anti-folate) to maximize the effectiveness of the treatment. 

What were your study objectives? 

Our primary objective was to determine the disease control rate of transarterial chemoperfusion treatment with cisplatin, methotrexate, and gemcitabine in patients with unresectable MPM using modified RECIST criteria.³ The secondary objectives were safety and tolerability, overall survival, and progression-free survival.

Tell us about the patient population.

To date, we’ve enrolled 27 patients. All patients underwent and failed multiple lines of chemotherapy (mean, 1.93 ± 1.3 lines). In addition, 4 patients had radiation therapy and 3 patients had pleurectomy. In other words, these patients were heavily pretreated and nonresponsive to treatment before enrollment in our study.

What was the treatment protocol?

The patients had laboratory workups and chest computed tomography every 4 weeks before treatment with transarterial chemoperfusion. Usually, one-third of the chemotherapy was delivered to the ipsilateral internal mammary artery and two-thirds to the descending thoracic aorta. The complication rate was very low, and most patients were pleasantly surprised that they did not experience the usual side effects from traditional IV chemotherapy.

Tell us about your study results and conclusions.

The disease control rate was very promising at 70%, with median overall survival at 8.5 months and median progression-free survival at 4.6 months. The median overall survival from disease diagnosis was 28.3 months. We therefore concluded that transarterial chemoperfusion treatment with triple chemotherapy is feasible and safe, with minimal side effects, in heavily pretreated MPM patients. 

Given the promising study results, do you foresee a time when transarterial chemoperfusion might become the first-line treatment for MPM?

At this point, it is unlikely that transarterial chemoperfusion will become a first-line therapy. As a patient, it is much easier to get an IV infusion or oral therapy (depending on the chemotherapy regimen) than to undergo an invasive procedure under sedation. In terms of invasiveness, this is similar to a cardiac catheterization or other arterial intervention. In addition, it is difficult to determine whether this is a viable first-line therapy because we are limited in the scope of our research by the small number of mesothelioma cases each year.

Any final thoughts?

Our study was based on the excellent results of Vogl et al, and their results have been even better in the ensuing years. However, in a sense, we’re comparing apples to oranges because their study was retrospective and this is a prospective analysis. We look forward to continuing our study and hope to answer some of these questions.

References

1. Kis B, Pereira M, Logeman J, et al. Transarterial chemoperfusion treatment of unresectable pleural mesothelioma – interim results of a phase 2 prospective study. 2020 SIR abstract poster #533. Available at https://www.sirmeeting.org. Accessed on 2020 July 7.

2. Vogl TJ, Lindemayr S, Naguib NNN, et al. Nonselective transarterial chemoperfusion: a palliative treatment for malignant pleural mesothelioma. Radiology. 2013;266:649-656.

3. Armato SG III, Nowak AK. Revised modified response evaluation criteria in solid tumors for assessment of response in malignant pleural mesothelioma (version 1.1). J Thorac Oncol. 2018;13:1012-1021. Epub 2018 May 9.

Address for Correspondence: Bela Kis, MD, PhD, Interventional Radiology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612. Email: Bela.Kis@moffitt.org