An immunomodulator that targets the PD-1 pathway effected sustained remission in 31% of patients who took it for advanced melanoma.
Remission lasted a median of 2 years, with 1- and 2-year overall survival of 62% and 43% respectively, wrote Dr. Suzanne Topalian and colleagues.
But perhaps even more exciting, they said, is that the benefit of nivolumab persisted for at least 16 weeks in all patients who had to discontinue therapy.
The report appeared in the March 3 issue of the Journal of Clinical Oncology.
"The persistence of partial tumor regression and stable disease ... suggests that PD-1 blockade may reset the immune equilibrium between tumor and host," wrote Dr. Topalian, director of the melanoma program at the Sidney Kimmel Comprehensive Cancer Center, Baltimore, and her coauthors.
The findings "are consistent with a mechanism by which an effective tumor-selective immune memory response may have been established in some patients, similar to immune memory against specific infectious organisms after antigen exposure," the investigators wrote (J. Clin. Oncol. 2014 March [doi:10.1200/JCO.2013.53.0105]).
PD-1 is an immune checkpoint that helps regulate the autoimmune action of activated T cells. Tumor cells can co-opt this pathway, using it to hide from T cell attack. Blocking PD-1 unmasks tumor cells, allowing the immune system to target them more effectively.
The 2-year follow-up study tracked response rates in 107 patients with advanced melanoma, who were part of a larger study of 306 patients with various solid-tumor cancers. The initial results of the phase I trial were reported at the 2013 meeting of the American Society of Clinical Oncology.
The new report focuses only on the patients with melanoma, who have completed treatment for at least 14 months, and up to 4 years. All of the patients had undergone two to five prior systemic treatments. They received up to 96 weeks of biweekly nivolumab infusions in varying doses.
Median progression-free survival was 3.7 months; 1- and 2-year progression-free survival rates were 36% and 27%, respectively.
About a third of the patients (33; 31%) experienced an objective response to the drug, with a median duration of 2 years. Fifteen of these (45%) occurred within the first 8 weeks of treatment, the investigators wrote. Of these responding patients, 19 (58%) were still responding when the data were analyzed, the authors noted.