Immunotherapy Combination Extends Mesothelioma Survival

Standard-of-care treatment for unresectable pleural mesothelioma cancer could be changing soon, sparked by a recently completed international study of a novel immunotherapy combination.

Patients in the randomized mesothelioma clinical trial who were treated with ipilimumab (Yervoy) and nivolumab (Opdivo) had a median overall survival of 18.1 months, compared to 14.1 months for those receiving chemotherapy.

The results of the mesothelioma trial, which was sponsored by Bristol Myers Squibb, were presented at the recent World Conference on Lung Cancer virtual meeting.

Authors of the study said it was the first time an immunotherapy combination used in a first-line setting for pleural mesothelioma improved survival in a large phase III clinical trial.

“Nivolumab and ipilimumab should be considered as a new standard of care,” said study presenter Dr. Paul Baas of the Netherlands Cancer Institute in Amsterdam. “This is a clear signal that this treatment could be of great use for these patients.”

Survival Benefit Greatest in Hard-to-Treat Mesothelioma Subtypes

While the survival improvement was modest overall, there was a dramatic improvement in the traditionally toughest-to-treat mesothelioma subtypes.

For patients with non-epithelioid histology (sarcomatoid or biphasic), median survival was 18.1 months for those receiving the immunotherapy treatment, and only 8.8 months for those receiving standard chemotherapy.

At 24 months, the overall survival rate for non-epithelioid histology was 38% for the immunotherapy group, but only 8% for the chemotherapy group.

“The difference was huge,” Baas said. “We are on the right track.”

According to the study authors, mesothelioma is the sixth different tumor type in which the immunotherapy combination has shown significant benefits over previous standard-of-care mesothelioma treatment.

Opdivo, Yervoy Harness the Immune System

The randomized study involved 605 patients at 114 different treatment centers, including 14 across the United States. Of those patients, 303 received the immunotherapy combination.

Both Opdivo and Yervoy are designed to better harness a patient’s own immune system in fighting the cancer, but they work in different ways and target different surface proteins.

The drugs have been used individually with various cancers, but with mixed results in earlier clinical trials for mesothelioma cancer.

Opdivo works by blocking a signal that prevents a patient’s T cells from attacking the cancer. Yervoy targets a protein receptor that downregulates the immune system.

Researchers believe there is a synergy between the two that could be a great benefit for several cancers.

Clinical Trial Shows Survival Advantages Vary

Patients receiving the immunotherapy were given Opdivo every two weeks and Yervoy every six weeks, for up to two years, depending upon disease progression.

Those patients receiving chemotherapy, which included pemetrexed (Alimta) and either cisplatin or carboplatin, were treated every three weeks until unacceptable toxicities or disease progression occurred.

Other notable findings from the study include:

Any treatment-related adverse side effects were found in 80% of the patients receiving immunotherapy and 82% receiving chemotherapy. Serious treatment side effects were found in 30% and 32%, respectively.

Side effects that led to treatment discontinuation occurred in 23% of the patients receiving immunotherapy, but only 16% of those getting chemotherapy.

“Malignant pleural mesothelioma is a devastating disease that has seen limited treatment advances over the past decade,” Dr. Sabine Maier, development lead of thoracic cancers at Bristol Myers Squibb, said in a statement earlier this year. “These topline results from the trial demonstrate the potential of Opdivo plus Yervoy in previously treated patients.”

The success of the combination was not a surprise, based upon earlier phase II studies that studied it in a second-line setting. Lancet Oncology published a study from France in 2019 that showed a median overall survival of 15.9 months and an average progression-free survival of 5.6 months.

Despite the optimism surrounding the combination, a diagnosis of unresectable pleural mesothelioma still comes with a poor prognosis. The five-year, overall survival for the disease is less than 10%.

“Selective targeting of non-epithelioid mesothelioma could further extend the benefit of ipilimumab and nivolumab for patients,” said Dr. Dean Fennell, University of Leicester in England, who was part of the study. “A new standard of care.”