Researchers study a new combination of immunotherapy for mesothelioma

Research and clinical trials

A recent study showed that the immunotherapy combination of trimlimumab and durvalumab showed surprising efficacy, particularly as a second-line treatment option for patients with pleural mesothelioma.

Its effectiveness, which is comparable to a similar group approved in 2020 by the US Food and Drug Administration, showed the new direction for the future treatment of mesothelioma.

Chemotherapy is no longer the standard, standalone treatment for most patients.

“Promising results have emerged regarding the use of targeted therapy with immune checkpoint inhibitors (ICI), particularly when given in combination regimens,” the study authors wrote. “The results of the study further support the efficacy of ICI combined therapy in mesothelioma.”

The Lancet Respiratory Medicine published the results of a phase II clinical trial conducted by the Department of Oncology at the University Hospital of Siena, Italy. Corresponding author Dr. Michael Mayo was not available to provide his view.

Medicines help the body target cancer cells

The study involved 40 patients who received intravenous trimlimumab and durvalumab every four weeks for four doses, followed by maintenance durvalumab for a further nine weeks.

The drugs are known as immune checkpoint inhibitors, a class of immunotherapy drugs that help a patient’s immune system fight cancer cells.

Durvalumab, also known by the brand name Imfinzi, works by blocking the PD-L1 protein that often allows cancer cells to bypass a patient’s immune system.

Tremelimumab complements durvalumab by blocking the receptors for immune cells that normally stop an immune attack.

At a follow-up of 52 months, five of the 40 patients were alive. More than a third of patients achieved an objective, long-term response.

Results included:

I examined options for re-immunotherapy

According to the authors, this was also the first study to measure the safety and efficacy of retreatment involving a combination of immune checkpoint inhibitory drugs.

Treatment with immunotherapy drugs is usually stopped in a clinical trial and not restarted once disease progression is detected.

17 of the 40 patients were part of the re-treatment phase in this study. Patients who had disease progression after partial response or stable disease were eligible for retreatment.

Survival at 12 months after retreatment was 52.9%, and 23.5% after 24 months. There were no serious immune-related adverse effects among the 17 patients.

For patients with mesothelioma who present with disease progression after an initial clinical benefit, retreatment with these same agents may be a beneficial option, the authors wrote.

Seven of the 17 patients in the retreatment group achieved stable immune-related disease. For three of these, stable disease lasted at least 11 months.

Median overall survival for those in the re-treatment group was 25.6 months, compared to only 11 months for those who received second-line chemotherapy.

The study authors concluded, “First-line combination therapy has been shown to significantly improve overall survival compared with platinum-based therapy for patients with pleural mesothelioma.” “It is likely to become the new standard of care in this situation worldwide.”

Researchers are also studying combination therapy

The same combination of two drugs is also being studied at Baylor College of Medicine in conjunction with severe surgery. The ongoing study hopes to determine whether durvalumab and tremelimumab, or durvalumab alone, are more effective with surgery.

Thoracic surgeon Dr. Brian Burt is the principal investigator on the Baylor study.

Durvalumab is part of an international phase III study measuring its effectiveness when used with the chemotherapy drugs pemetrexed and cisplatin. The immunotherapy drug was first approved by the Food and Drug Administration in 2017 for bladder cancer and has shown early effectiveness with some types of lung cancer.

Among the US portion of the trial are the Seattle Cancer Care Alliance, the Stanford Cancer Institute in Palo Alto, California, and Fox Chase Cancer Center in Philadelphia.

While immunotherapy has been successful for some mesothelioma patients, it has not usually been effective for the majority, creating the need to determine who would benefit best before starting treatment.

The authors in Italy believe this latest study could help serve this purpose – identifying tumor mutational burden as a potential marker for immune checkpoint inhibitor drugs.

“A higher mutational load at baseline appears to determine which patients with mesothelioma are most likely to benefit from ICSI and retreatment with these agents,” the researchers wrote. “This finding is intriguing and needs further exploration.”

They also believe that the use of immunotherapy to treat mesothelioma will grow exponentially in the coming years. The U.S. Food and Drug Administration approved nivolumab and ipilimumab as a combined treatment in 2020, the first new treatment option for mesothelioma in nearly two decades.

“Anti-tumor immunotherapy with the immune checkpoint immunosuppressant in patients with mesothelioma has not yet reached its full potential,” the study authors wrote. “Further investigations are warranted for the potential application of reprocessing in clinical practice.”