Immune Checkpoint Inhibitor May Change the Standard Treatment of Malignant Pleural Mesothelioma

The immune checkpoint inhibitor durvalumab could become a standard part of first-line mesothelioma treatment if the results of a new study hold true in a Phase 3 trial. 

Australian researchers have become the latest to show the benefit of adding durvalumab to first-line chemotherapy for pleural mesothelioma.

Chemotherapy is usually the first thing doctors use to treat pleural mesothelioma. But as many as half of mesothelioma patients do not respond to it. Researchers around the world are hopeful that adding an immune checkpoint inhibitor like durvalumab will lead to better response rates.

What is an Immune Checkpoint Inhibitor?

Mesothelioma cells survive and thrive in part because they have ways of protecting themselves. Chemotherapy drugs are less likely to hurt them than healthy cells. Cancer cells are also less likely to be seen as a threat by the immune system than other kinds of invaders. This makes malignant mesothelioma very difficult to treat.

One way mesothelioma cells protect themselves is with the protein PD-1. An immune checkpoint inhibitor like durvalumab blocks PD-1. Without it, cancer cells become more vulnerable and other treatments may work better. 

Durvalumab (IMFINZI), pembrolizumab (Keytruda), and nivolumab (Opdivo) are immune checkpoint inhibitors that block PD-1. Studies suggest that these drugs can improve response to chemotherapy. The key now is to find out which one works best for mesothelioma and at what dose.

Testing Durvalumab with Mesothelioma Chemotherapy

Pleural mesothelioma is rare. It usually only happens in people who have worked or lived around asbestos. As a result, most mesothelioma studies are small. 

The latest immune checkpoint inhibitor study enrolled 54 mesothelioma patients from nine Australian hospitals. It went by the acronym DREAM. Patients were not eligible for surgery and had not yet received chemotherapy.

Study subjects got durvalumab along with standard mesothelioma chemotherapy on the first day of each round of treatment. They could have up to six cycles of chemotherapy. Patients could stay on the immune checkpoint inhibitor for up to a year. 

Results Warrant Further Study

Researchers followed the patients’ progress for a median of 28 months. At six months, 31 patients (54 percent) were alive with no tumor growth. Some of the patients experienced a drop in white blood cell counts, nausea, or anemia. But none of them died because of the treatment. 

“The combination of durvalumab, cisplatin, and pemetrexed has promising activity and an acceptable safety profile that warrants further investigation in a randomised phase 3 trial,” the report concludes. 

A Phase 3 trial of this immune checkpoint inhibitor for pleural mesothelioma is already in the works in the US. Earlier this year, researchers at Johns Hopkins showed that durvalumab and chemotherapy improved mesothelioma survival. Patients in that Phase 2 study had an overall survival of 20.4 months. Most mesothelioma patients live about a year. 

The Johns Hopkins team plans to start recruiting for the Phase 3 trial later this year.  

Sources:

Nowak, AK, et al, “Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in”, September 2020, The Lancet Oncology, https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30462-9/fulltext

“Research Story Tip: Chemotherapy/Immunotherapy Combo Shows Promise for First-Line Treatment of Mesothelioma”, Johns Hopskins new release, June 11, 2020, https://www.hopkinsmedicine.org/news/newsroom/news-releases/research-story-tip-chemotherapyimmunotherapy-combo-shows-promise-for-first-line-treatment-of-mesothelioma