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New Combination Therapy for NSCLC Tested in Phase II Trial

By: Celeste L. Dixon
Posted: Tuesday, March 12, 2019

The first report of a randomized, placebo-controlled, phase II trial evaluating an epigenetic agent (CC-486; oral azacitidine) plus immunotherapy (pembrolizumab) in patients with previously treated, advanced non–small cell lung cancer (NSCLC) was published in the European Journal of Cancer. No statistically significant differences in progression-free or overall survival were found between the 51 patients in the pembrolizumab + CC-486 cohort and the 49 patients in the pembrolizumab plus placebo cohort.

The scientific rationale for the study, according to Benjamin P. Levy, MD, of Johns Hopkins Sidney Kimmel Cancer Center, Washington, DC, and colleagues, was that “emerging evidence supports the critical role of epigenetic silencing in impairing tumor immunogenicity by suppressing antigen processing and presentation and tumor-associated antigen expression.”

The lack of improvement in progression-free survival (the primary endpoint) in the CC-486 arm may be due to decreased treatment exposure as a result of gastrointestinal adverse effects linked to CC-486, speculated the investigators. Alternately, “the combination [may have been] antagonistic in this patient population. For example, treatment with azacitidine could have upregulated immune checkpoints in the tumor microenvironment, negatively regulating T-cell activity,” they wrote.

What would help in creating potentially useful combinations for future trials would be identifying biomarkers that characterize both the tumor and immune status, Dr. Levy and colleagues concluded. An important goal is to extend the median survival of patients with advanced NSCLC: Real-world studies, the team noted, indicate that it is currently 5 to 13 months after initiation of second-line treatment.

Disclosure: The study authors’ disclosure information may be found at ejcancer.com.



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