Real-World Study Evaluates Outcomes With Ipilimumab and Nivolumab in Mesothelioma

Arthi Sridhar, MD, of the University of Texas Southwestern Medical Center, discusses a real-world multicenter retrospective study of treatment outcomes with ipilimumab and nivolumab in mesothelioma that was presented at the IASLC 2024 World Conference on Lung Cancer.

The regimen is currently approved for the frontline management of unresectable mesothelioma based off the CheckMate 743 study of the combination.  It was important to conduct the real-world study because there is “a paucity of data regarding these patients outside of a clinical trial, given how rare the disease is,” Dr. Sridhar said.

To address the knowledge gap, the study aimed to describe survival outcomes and immune-related adverse events in patients receiving ipilimumab and nivolumab in a real-world setting. Dr. Sridhar and colleagues identified 90 patients who received the combination in the front-line setting and 36 who received it after progression. Most patients had pleural mesothelioma, with peritoneal mesothelioma being the second most common form. Epithelioid histology was the most common subtype.

“The patient population that we were able to identify was very reflective of the population that is impacted by this disease,” Dr. Sridhar said.

The study showed no significant differences in progression-free survival (PFS) between patients receiving ipilimumab and nivolumab as a frontline treatment (median PFS, 7.9 months), and those receiving it after progression (median PFS, 8.4 months; P=0.67).

“The results were actually similar to what was found in Checkmate 743, where the progression-free survival of patients who received this combination upfront was about 6.8 months,” Dr. Sridhar said.

There was also no difference between groups in overall survival (OS), with a median OS of 14.83 months in patients receiving ipilimumab and nivolumab in the frontline and a median OS of 28.9 months in those receiving the combination after progression (P=0.49).

“The overall survival in the real-world study of 14.8 months is actually less when you compare it to the Checkmate 743 trial, where it was about 18 months,” Dr. Sridhar pointed out. “When it comes to understanding how the survival… was numerically so much more in the prior-line group, we think that this can be explained by a smaller sample size in the prior-line group and a potential selection bias by nature of the design of this study.”

The study also evaluated immune-related adverse events in the real-world setting, finding these events occurred in 44% of patients receiving ipilimumab and nivolumab as a frontline therapy, compared to 56% of those receiving it after progression. Immune-related adverse events of grade 3 or 4 accounted for 25% of the toxicities in the frontline and 40% of the toxicities in those receiving the combination therapy after progression.

“It’s also interesting to note that patients who received immune checkpoint inhibition in the frontline setting for unresectable mesothelioma experience lower immune-related adverse events than the prior lines group,” she said. “That is something that we want to double-click on and look further into as we progress in the study.”

Dr. Sridhar explained that this real-world data on immune-related adverse events with ipilimumab and nivolumab has key clinical implications for patients with mesothelioma.

“The study does highlight the benefits of receiving frontline dual checkpoint inhibition in terms of tolerability,” she said. “It is important because patients who are diagnosed with mesothelioma are generally an older population and weighing the risks versus benefits in terms of tolerability then becomes a very important question.”

The next steps with the research are to expand the sample size by gathering data from additional patients receiving the combination therapy in the frontline setting and after progression. The researchers also plan to add a third historical control arm that includes patients who received chemotherapy alone.

“With this information, we’re really hoping to improve the power of the study and the validity of the study,” Dr. Sridhar said.

She concluded by reflecting on the importance of real-world data on the use of ipilimumab and nivolumab as a frontline therapy and after progression in patients with unresectable mesothelioma.

“The truth is, is that even though it is [approved for] frontline, not everybody chooses to give it to patients right up front,” Dr. Sridhar said. “People sometimes want to keep it in their back pocket, try chemotherapy first… I think it’s important to understand the nuances in the differences and outcomes between patients in these two settings because that is what real world is, it is what people do.”