After 3 years, 23% of patients who received combination immunotherapy were still alive, in comparison with 15% of patients in the chemotherapy arm.
Combination immunotherapy continued to provide a “durable and long-term benefit” compared with chemotherapy, commented Solange Peters, MD, from the Oncology Department, Center Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The new data from the additional 12 months of follow-up “confirm nivolumab plus ipilimumab as a standard of care for unresectable MPM, regardless of histology,” she commented.
She presented the update on September 17 at the annual meeting of the European Society of Medical Oncology (ESMO). She is the current president of the organization.
Previously, 2-year data from this study showed that the combination yielded a median overall survival of 18.1 months, compared to 14.1 months with standard-of-care chemotherapy.
As reported by this news organization, this translated into a 26% improvement in overall survival; 41% of patients in the immunotherapy arm were still alive at 2 years, versus 27% in the chemotherapy group.
On the basis of these data, the combination was subsequently approved in the United States, the European Union, and elsewhere for the first-line treatment of adults with unresectable MPM.
The new data come from a 3-year update, as well as an exploratory biomarker analysis. The new data show significantly improved overall survival with the combination immunotherapy. Among those who responded to immunotherapy, response was ongoing for 28% of patients at 3 years.
Benefit was seen even for patients who discontinued the treatment because of treatment-related adverse events, indicating that discontinuance does not appear to have a negative impact on the long-term benefits, Dr. Peters commented.
In addition, the new analysis suggested that patients with a high score on a four-gene inflammatory signature did particularly well with nivolumab plus ipilimumab, whereas chemotherapy patients did worse if they had nonepithelioid disease, a finding not seen with immunotherapy.
The discussant for this abstract, Pilar Garrido, MD, PhD, associate professor of medicine at the Universidad de Alcalá, Madrid, said that despite the impressive findings, there is a “critical need” to establish predictive biomarkers in MPM.
This is particularly pressing in cases involving early progression, inasmuch as median progression-free survival (PFS) in CheckMate 743 was similar overall, and chemotherapy performed better than immunotherapy in the first 8 months.
There is also a need to be able to identify patients who will have an ongoing response at 3 years, as well as to clarify the impact of toxicity, given that the median duration of response was 20 months following discontinuation of treatment after just 4 months.
Dr. Garrido cautioned that the exploratory analyses were of “limited value,” because RNA data for the gene signature analysis were available for only 54% of patients, and the study was not powered to detect differences on the basis of programmed cell death–ligand-1 (PD-L1) expression.
Summarizing, Dr. Garrido said that although the current results showed that combination immunotherapy “continued to provide” a survival benefit in “a subgroup of patients,” the “better characterization of predictive biomarkers” will be “crucial” to improving these results.