Immunotherapy: Promising Results for Mesothelioma Treatment

Malignant pleural mesothelioma is an aggressive and rare cancer primarily caused by exposure to asbestos. For many years, treatment options for this disease have typically been limited to surgery, radiation therapy, and chemotherapy, and the prognosis is generally poor.  Immunotherapy has been used more frequently to treat mesothelioma over the last three years.  

A recent clinical trial called CheckMate 743 demonstrated encouraging results for immunotherapy treatment versus traditional chemotherapy for patients with advanced malignant pleural mesothelioma (MPM). These findings suggest immunotherapy is more effective for many mesothelioma patients and their healthcare providers. 

Details and Outcomes

The study followed 605 patients with MPM who had not previously received treatment for the disease and randomly assigned them to two groups: one receiving the immunotherapy treatment (nivolumab – sold under the brand name Opdivo – combined with ipilimumab – sold under the brand name Yervoy) and the other group receiving chemotherapy. The median period of the immunotherapy treatment was 5.6 months and 3.5 months for chemotherapy, with the researchers following up with patients for a minimum of three years.

Across the board, patients in the immunotherapy treatment group showed statistically significant improved outcomes compared to those in the chemotherapy group.

• The overall survival rate after three years for patients treated with immunotherapy was 23%, compared to 15% in the chemotherapy group.
• The median overall survival time was 18.1 months in the immunotherapy group, compared to 14.1 months in the chemotherapy group.
•  In the immunotherapy group, 14% of patients did not experience progression of the disease, compared to 1% in the chemotherapy group.

The study also compared results for patients with epithelial mesothelioma, the most common type of the disease, and those with non-epithelial forms. 

• The immunotherapy group showed improved three-year survival rates for both types —24% for epithelial and 22% for non-epithelial. 
• In contrast, three-year survival rates for patients in the chemotherapy group were 19% for those with epithelial mesothelioma and 4% with a non-epithelial form.  In other words, significantly better results when treating sarcomatoid or biphasic mesothelioma with immunotherapy vs. chemotherapy.

Side Effects

Treatment-related adverse effects from mesothelioma therapies can be unpleasant or even cause patients to stop the therapy. Doctors must weigh the benefits and risks of any treatment options for their patients.

Treatment-related side effects of the immunotherapy treatment were consistent with previous studies. The most common were diarrhea, itchy skin (pruritis), and rash. These caused 23% of the patients to stop part of the treatment and 17% to completely cease the therapy. However, discontinuing the treatment did not negatively impact the long-term survival benefit.  Many doctors believe that the side effects for immunotherapy are less than chemotherapy.  

Insights in too Potential Gene-Targeted Applications

Although exploring biomarkers to predict treatment outcomes was not a focus of the trial, the researchers identified some interesting implications. Other studies on cancer treatment have identified a genetic signature that shows potential for targeted therapies. In the CheckMate 743 trial, a high score for that signature appeared to suggest improved survival in the immunotherapy group. 

In contrast, the expression of a gene known as PD-L1 is a well-established biomarker for predicting response to immunotherapy in certain types of cancer. Although overall survival for patients undergoing immunotherapy in the trial was similar regardless of the gene expression, it was longer for patients in the chemotherapy group with the expression. 

While these results are far from definitive, they pave the way for possible future studies and trials on gene-targeted treatments for MPM.

New Hope for Mesothelioma Patients

These findings provide robust evidence supporting the use of immunotherapy in MPM and challenging the traditional chemotherapy approach. Based on these results, nivolumab plus ipilimumab was approved for first-line treatment of unresectable MPM in the United States, the European Union, and other countries. 

With improved outcomes and largely manageable side effects, nivolumab plus ipilimumab combination therapy offers an encouraging alternative for MPM patients and represents meaningful progress in the ongoing search for more effective treatments that support a better quality of life.