Study details
Dr. Peters reminded the audience that the CheckMate 743 trial involved patients with unresectable MPM who had not previously received any systemic therapy and who had a good performance status.
A total of 605 patients were enrolled. They were randomly assigned in a 1:1 ratio to receive either nivolumab plus ipilimumab for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin.
The median age of the patients was 69 years, and 77% were men. The baseline characteristics were well balanced between the two treatment groups; 75% to 76% had epithelioid disease, and for 74% to 80% of patients, baseline PD-L1 expression was greater than or equal to 1%.
Subgroup analysis indicated that combination immunotherapy was beneficial regardless of patient age, sex, performance status, and smoking status.
However, the new analysis suggested that the improvement in overall survival depended on PD-L1 expression, at a hazard ratio for combination immunotherapy versus chemotherapy of 0.71 in patients with expression of greater than or equal to 1%, compared with 0.99 for patients with expression of less than 1%.
Dr. Peters explained that the performance of nivolumab plus ipilimumab was identical in both PD-L1 expression groups, but it was the chemotherapy arm that performed markedly better for patients with expression of less than 1%.
An inverse finding was observed when patients were stratified by tumor histology.
In those with epithelioid disease, the median overall survival with combination immunotherapy was 18.2 months, versus 16.7 with chemotherapy, at a hazard ratio of 0.85.
At 36 months, 24% of immunotherapy patients were still alive, as were 19% of those given standard-of-care chemotherapy.
Among patients with nonepithelioid disease, however, median overall survival was 18.1 months with nivolumab plus ipilimumab, versus just 8.8 months with chemotherapy, at a hazard ratio of 0.48. At 3 years, 22% of patients who received combination immunotherapy were still alive, compared with 4% of those who received chemotherapy.
Other results showed that PFS was only slightly longer with combination immunotherapy, at 6.8 months versus 7.2 months, for a hazard ratio of 0.92.
Yet at 36 months, 14% of patients who received nivolumab plus ipilimumab had not experienced disease progression, versus just 1% of those in the chemotherapy arm.
This difference was even more pronounced when the researchers assessed objective response rates: 28% of patients who received combination immunotherapy were still responding at 36 months, versus 0% among patients given chemotherapy.
This translated into a median duration of response of 11.6 months for nivolumab plus ipilimumab, versus 6.7 months with chemotherapy.
The safety assessment showed that rates of treatment-related adverse events of any grade and of grade 3-4 were similar between the combination immunotherapy and chemotherapy arms.
However, rates of treatment-related adverse events that led to discontinuation of all components of the regimen were higher with immunotherapy, at 17% for events of any grade and 13% for events of grade 3-4, compared with 8% and 5%, respectively, with chemotherapy.
Serious treatment-related adverse events were more common with nivolumab plus ipilimumab. Events of grade 3-4 occurred in 13% of patients with nivolumab plus ipilimumab, versus 5% with chemotherapy.
Dr. Peters showed that this did not severely affect overall survival, however. Among patients who discontinued combination immunotherapy, the median duration of response was 20.0 months.
Median overall survival in these patients was 25.4 months, and the 3-year overall survival rate was 37%.
The study was funded by Bristol-Myers Squibb. Dr. Peters and Dr. Garrido reported relationships with numerous sources in industry.
A version of this article first appeared on Medscape.com.