Five-Year Study Confirms Lasting Benefits of Immunotherapy for Mesothelioma

Key findings

Five years after treatment, 14 percent of patients who received immunotherapy were alive, compared with 6 percent of those treated with chemotherapy.
Among patients with epithelioid mesothelioma, five-year survival reached 14 percent with immunotherapy versus 8 percent with chemotherapy.
For patients with non-epithelioid mesothelioma, five-year survival was 12 percent with immunotherapy and only 1 percent with chemotherapy.
Median overall survival was 18.1 months with nivolumab plus ipilimumab, compared with 14.1 months for chemotherapy.
Tumor response occurred in about 39 percent of patients receiving immunotherapy and 44 percent receiving chemotherapy.
Seventeen percent of immunotherapy responders still had an ongoing response five years later.

A newly released five-year analysis from the landmark CheckMate 743 clinical trial provides encouraging evidence that immunotherapy can produce long-term survival for some people with unresectable pleural mesothelioma. The study results, highlighted by oncology news outlet OncoDaily and published in the Journal of Clinical Oncology, show that a combination of two immune checkpoint inhibitors continues to outperform traditional chemotherapy over time.

Pleural mesothelioma is a rare cancer that develops in the lining of the lungs and is strongly associated with asbestos exposure. For many years, treatment options were limited and long-term survival was uncommon. The updated results from CheckMate 743 suggest that immunotherapy is helping to change that outlook for some patients.

Comparing immunotherapy with chemotherapy

The CheckMate 743 trial evaluated the combination of nivolumab and ipilimumab as a first-line treatment and compared it with the standard chemotherapy regimen of pemetrexed (Alimta) together with cisplatin or carboplatin. Researchers tracked patient outcomes for a median follow-up period of nearly 67 months, providing the longest observation period yet for a first-line immunotherapy approach in pleural mesothelioma.

Investigators reported that the immunotherapy combination continued to demonstrate a survival advantage. As the researchers wrote in the journal article, “nivolumab plus ipilimumab demonstrated continued overall survival benefit versus chemotherapy in all randomly assigned patients.”

At the five-year mark, 14 percent of patients who received the immunotherapy regimen were still alive. In contrast, only 6 percent of patients treated with chemotherapy reached that milestone. The hazard ratio for overall survival was 0.74, meaning the risk of death was reduced by roughly 26 percent in the immunotherapy group.

Survival differences by tumor type

Mesothelioma is often categorized by histology, or tumor type. The most common form, epithelioid mesothelioma, typically responds somewhat better to treatment than the more aggressive non-epithelioid forms.

In the updated analysis, patients with epithelioid tumors experienced a five-year survival rate of 14 percent when treated with nivolumab plus ipilimumab, compared with 8 percent among those who received chemotherapy.

The contrast was even more pronounced in patients with non-epithelioid disease. In this group, five-year survival reached 12 percent with immunotherapy but only 1 percent with chemotherapy. The hazard ratio for overall survival among these patients was 0.48, suggesting a substantially lower risk of death when the immunotherapy combination was used.

Median survival and long-term outcomes

Median overall survival, which reflects the point at which half of patients are still alive, was 18.1 months for those treated with nivolumab plus ipilimumab. Patients who received chemotherapy had a median survival of 14.1 months.

Although these figures may appear modest, they represent progress in a cancer that has historically been difficult to treat. Median survival does not represent an average life expectancy. Instead, it marks the midpoint of the survival curve. Many patients may live longer than that value, and some significantly longer.

The five-year survival rate seen with immunotherapy is particularly notable given the historically low rates of long-term survival in mesothelioma.

Tumor responses and durability

Initial response rates were relatively close between the two treatment approaches. About 39 percent of patients receiving nivolumab plus ipilimumab experienced tumor shrinkage, compared with 44 percent of those treated with chemotherapy.

However, the durability of those responses differed dramatically.

Among patients whose tumors responded to immunotherapy, 17 percent continued to show a response five years later. In the chemotherapy group, none of the responders maintained an ongoing response at the five-year mark.

This pattern suggests an important distinction between the treatments. Chemotherapy may produce faster tumor shrinkage in some patients, but immunotherapy appears capable of generating longer-lasting control in a subset of cases.

Investigating potential biomarkers

Researchers also explored whether certain blood-based indicators might help predict which patients benefit most from immunotherapy. One area of focus involved monocytic myeloid-derived suppressor cells, often abbreviated as M-MDSCs.

These immune cells are believed to interfere with the body’s anti-cancer immune response and may limit the effectiveness of immunotherapy. The study found that patients who had higher levels of M-MDSCs at the start of treatment tended to experience poorer overall survival when treated with nivolumab plus ipilimumab.

Specifically, the hazard ratio for overall survival was 1.25 among patients with higher baseline levels compared with those who had lower levels. Researchers emphasized that this analysis is exploratory and will require additional study before such markers could guide treatment decisions.

Accounting for treatment crossover

Another factor examined in the analysis involved patients who switched treatments during the study. About 24 percent of participants who initially received chemotherapy later went on to receive immunotherapy.

To better understand the true effect of starting immunotherapy first, investigators performed an adjusted statistical analysis that accounted for this crossover. After making that adjustment, the hazard ratio for overall survival improved to 0.64 in favor of nivolumab plus ipilimumab.

The adjusted analysis also reduced the estimated median survival for the chemotherapy group to 12.1 months, further emphasizing the benefit associated with beginning treatment with immunotherapy.

Safety findings remain consistent

The extended follow-up period did not reveal any new safety concerns. According to the study authors, “no new safety signals were observed” during the longer observation period.

Immune checkpoint inhibitors can still cause immune-related side effects, which may affect organs such as the lungs, liver, or thyroid. However, the safety profile reported in the five-year update was consistent with what had been observed earlier in the trial.

A meaningful step forward

In their concluding remarks, the investigators noted that the updated data show sustained, long-term clinical benefits from nivolumab plus ipilimumab when used as a first-line treatment for pleural mesothelioma. The survival advantage was observed regardless of tumor histology.

As a result, the findings further reinforce the role of the immunotherapy combination as a standard treatment option for patients with unresectable pleural mesothelioma.

For individuals and families facing this diagnosis, the results do not represent a cure. Still, the ability of a therapy to help a portion of patients live five years or longer is a meaningful advance in a disease where durable survival has historically been rare.

Ongoing research will continue to explore how immunotherapy can be improved, identify which patients benefit most, and determine how new treatment strategies might build on the progress already achieved.