Immunotherapy Shows Promise in Tough-to-Treat Mesothelioma

CHICAGO -- Immunotherapy may offer new options as second-line treatment for patients with malignant pleural mesothelioma (MPM), researchers reported here.

In patients with histologically proven relapsing MPM, the median overall survival (OS) with single-agent nivolumab (Opdivo) was 10.4 months, while the median OS with the combination of nivolumab and ipilimumab (Yervoy) has not been reached, according to Arnaud Scherpereel, MD, PhD, of the University Hospital of Lille in France, and colleagues.

"Our findings suggest that immunotherapy may provide new hope to patients with relapsed mesothelioma," he said at the American Society of Clinical Oncology (ASCO) annual meeting. "This randomized phase II trial may be enough to support the use of immune checkpoint inhibitors in this setting, but it is too early to conclude whether nivolumab alone or in combination with ipilimumab is better."

In the study, 63 patients diagnosed with relapsed MPM following chemotherapy (1-2 prior lines) were assigned to treatment with nivolumab, while 62 patients received both agents. Most had a a good performance status (0-1) and had been diagnosed with epithelioid MPM.

In patients that were evaluable, tumor shrinkage was observed in 18% of patients on nivolumab and in 26% of patients on the combination. Those who received the single agent achieved a median progression-free survival (PFS) of 4 months versus 5.6 months PFS for those who received the combination.

Severe side effects were seen in 10% of the patients in the single-agent arm, and 18% in the combination arm.

There were more adverse events with combination treatment, Scherpereel said at an ASCO press conference, including deaths of three patients, which were possibly treatment related. One died of fulminant hepatitis, one from metabolic encephalopathy, and one from acute renal failure, Scherpereel told MedPage Today.

Paul Bunn Jr., MD, of the University of Colorado Anschutz Medical Campus in Aurora, told MedPage Today, "chemotherapy has been the initial standard treatment for mesothelioma, but there really has been no standard second-line treatment. Now it looks like we have two possible therapies."

Bunn, who was not involved in the study, said more research is needed on when immunotherapy should be used, and for how long. "There were three patients who died when they received nivolumab plus ipilimumab," he noted. "There is a question of whether you should [give] ipilimumab for 4 cycles, and then stop and continue with single-drug treatment. In this study, they continued [on both agents], which undoubtedly led to greater toxicity. In general, the side effects should be manageable."

ASCO expert Michael Sabel, MD, of the University of Michigan in Ann Arbor noted that "mesothelioma is a very difficult cancer to treat, and has very poor success rates with chemotherapy. In this study, we saw rather dramatic responses to immunotherapy."

However, he cautioned that it was "too early to say that these results set a new standard of care, but this study may set the pathway for further examination. I think we are well on the route that this may become an available option for patients with mesothelioma."

Yanis Boumber, MD, PhD, of the Fox Chase Cancer Center in Philadelphia agreed that MPM was a treatment challenge, "with average survival of about 1 year. No significant progress has occurred since the 2004 approval of pemetrexed in this disease. Patients who progressed or recurred after pemetrexed and platinum chemotherapy have limited treatments options."

He added that "typically, second-line chemotherapy has a less than 10% chance to shrink mesothelioma, with average time until cancer worsens of 1-2 months and expected survival of less than 5-6 months."

"These early results with immunotherapy are clearly a breakthrough, giving us hope to an effective treatment option, and a possibility to cure some patients with this aggressive disease in the near future," said Boumber, who was not involved in the study.

Sabel echoed his praise for immunotherapy. "I think it is really amazing that immunotherapy is now showing dramatic responses in tumors that we never really suspected would be susceptible to immunotherapies. For many years, we thought this therapy would be confined to melanoma and renal cell cancer, but now we are seeing successes in tumors which would not have been predicted," he noted.