Avelumab Might Offer Mesothelioma Patients Hope by Blocking PD-L1

A treatment strategy being tested by scientists to combat mesothelioma involves the disruption of protein PD-L1. Among the drugs showing the most promise so far for disrupting PD-L1 is avelumab.

Results of recent tests with avelumab were shared at the American Society of Clinical Oncology annual meeting held in Chicago in early June. The results were detailed in a presentation delivered by Raffit Hassan, M.D., of the National Cancer Institute in Bethesda, Maryland.

According to Hassan, avelumab showed clinical activity and was generally well tolerated by mesothelioma patients in a Phase I trial of the novel therapeutic.

Mesothelioma Aided by Programmed Cell Death-Ligand 1

PD-L1 is properly known as programmed cell death-ligand 1. Approximately 20 percent of patients produce the PD-L1 protein. Among those patients, PD-L1 shows up alarmingly often in those whose mesothelioma is of the sarcomatoid type.

Sarcomatoid mesothelioma owns a reputation for being more resistant to treatment than either of the other two types of mesothelioma – biphasic and epithelioid.

PD-L1 suppresses your body’s natural response to the presence of mesothelioma. So, instead of knocking down mesothelioma cells, PD-L1 causes your immune system to largely ignore the cancer’s presence.

The idea behind avelumab is to disrupt PD-L1 activity so that the protein cannot interfere so easily with immune system functioning. This should then make the immune system better able to kill mesothelioma cells.

The testing of avelumab described by Hassan involved 53 mesothelioma patients with either the pleural or peritoneal form of it. All of them had mesothelioma too far advanced for treatment with surgery.

Avelumab was given to these patients for a number of months. Half the patients were younger than 66 and half were older. All of them had undergone some form of mesothelioma treatment in the past.

Nearly three-quarters of the patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 1.

Avelumab Benefitted Some Mesothelioma Patients

Hassan reported that there were five patients who had a partial response to the avelumab. He said the response was ongoing for four of them.

Avelumab caused 25 of the patients — about 47 percent of the total group — to achieve disease-stable status. He said the disease control rate was 56.6 percent.

As for progression-free survival, the median was just over 17 weeks. Measurements taken at 24 weeks revealed that 38.4 percent of the patients were enjoying progression-free survival.

The researchers in charge of this study divided the patients into those who were PD-L1 positive and those who were PD-L1 negative. Thirty-five percent of the evaluable patients turned out to be PD-L1 positive.

Hassan said that PD-L1 positive patients given avelumab had an objective response rate of 14.3 percent. PD-L1 negative patients had an objective response rate of 8 percent.

Also, PD-L1 positive patients had a median progression-free survival of 17.1 weeks. But PD-L1 negative patients achieved a median of only 7.4 weeks.

Treatment-related adverse events occurred in 41 patients. The most common of these were grade 1 or 2 infusion-related reactions, fatigue, chills and pyrexia. Grade 3 or higher adverse reactions affected four patients.

“Ongoing follow-up will further characterize durability of the clinical benefit,” Hassan said. “This dataset is the largest study to date of patients with mesothelioma treated with an…anti–PD-L1 antibody.”

The title of the presentation delivered by Hassan was “Avelumab Promising in Unresectable Mesothelioma.”