Experimental Chemotherapy Improves Survival for Biphasic and Sarcomatoid Mesothelioma

A novel type of chemotherapy studied in a clinical trial improved the survival of people with certain types of mesothelioma.

Pegargiminase is an arginine-blocking chemotherapy used in a clinical trial spanning five countries, including the United States and the United Kingdom. 

The study was for people with biphasic mesothelioma and sarcomatoid mesothelioma cell types, which are more difficult to treat than the epithelioid mesothelioma cell type. Pegargiminase was combined with the standard, FDA-approved combination of mesothelioma chemotherapy: pemetrexed and cisplatin

Adding pegargiminase to the chemotherapy regimen improved the median survival by 1.6 months and quadrupled the 36-month (3-year) survival rate compared to people who only received pemetrexed and cisplatin without pegargiminase.

 

Treatment for Biphasic Mesothelioma and Sarcomatoid Mesothelioma

There are three cell types of mesothelioma: epithelioid, biphasic and sarcomatoid. Epithelioid mesothelioma is typically more responsive to treatment because the cells are easier to distinguish on scans and can be removed more effectively during surgery. The prognosis for epithelioid mesothelioma is the best of the three cell types, usually close to two years.

By contrast, sarcomatoid mesothelioma is the toughest of the cell types to treat. The cells are erratic and difficult to identify on scans and during surgery. Most doctors will not recommend surgery as a treatment option for people with sarcomatoid mesothelioma. The prognosis for this cell type is also the least promising, usually an estimated 8 months.

Biphasic mesothelioma is a mixture of epithelioid and sarcomatoid cells, and the prognosis and treatment effectiveness depends on the ratio of the cells.

Doctors have long sought a new approach for treating cases of nonepithelioid mesothelioma since chemotherapy, immunotherapy and radiation therapy can add a few months to patients’ life expectancies but offer little as a long-term solution.

Adding pegargiminase to standard chemotherapy treatment for nonepithelioid mesothelioma cases was the focus of the study.

 

How Does Pegargiminase Work?

Pegargiminase works by depriving arginine for tumors that lack argininosuccinate synthetase (ASS) expression. ASS is a key enzyme which converts citrulline to arginine. Tumors that usually do not express ASS include melanoma, hepatocellular carcinoma, some renal cell cancers and some mesotheliomas.

Many cancer cells have deficiencies in arginine metabolic pathways and rely on the uptake of arginine for rapid metabolism and proliferation. This makes some cancer cells vulnerable to the deprivation of arginine, which is the purpose of pegargiminase.

 

More Details of the Clinical Trial

The clinical study, titled ATOMIC-Meso, was a phase 3 trial featuring 249 people with nonepithelioid mesothelioma (biphasic mesothelioma or sarcomatoid mesothelioma). The trial was conducted at 43 medical centers from August of 2017 to August of 2021.

The median survival for patients receiving pegargiminase plus chemotherapy was 9.3 months. The median survival for patients receiving only chemotherapy was 7.7 months. Other notable statistics from the study were:

• Pegargiminase led to a median progression-free survival of 6.2 months, about one month more than without the treatment.
• Pegargiminase led to a 3-year survival rate of 11.9%, compared to 3.3% for people who didn’t receive the treatment.

The treatment was also safe and well-tolerated among patients.