Epigenetic Therapy Shows Promise in Progressive NSCLC

Demethylation of epigenetically silenced genes associated with lung cancer seen in blood samples

THURSDAY, Nov. 10 (HealthDay News) -- Epigenetic therapy combined with low-dose azacitidine and entinostat is well-tolerated and provides an improvement in median survival similar to existing therapies for patients with metastatic non-small-cell lung cancer (NSCLC), according to a study published online Nov. 9 in Cancer Discovery.

Rosalyn A. Juergens, M.D., from Johns Hopkins University in Baltimore, and colleagues conducted a phase I/II trial to assess the safety, tolerability, and efficacy of epigenetic therapy combined with azacitidine and entinostat in extensively pretreated patients with recurrent metastatic NSCLC. The phase I trial assessed adverse events with the combination including 30 or 40 mg/m²/day azacitidine. The phase II trial evaluated the response rate of the combination at 40 mg/m²/day of azacitidine.

The investigators found that the epigenetic therapy was well-tolerated with objective responses. One patient remained alive and without disease progression (complete and partial response) approximately two years after completing the therapy. The treatment compared favorably with existing therapeutic options, with a median survival of 6.4 months in the entire cohort. Serial blood samples of these patients showed demethylation of a set of four lung cancer-associated epigenetically silenced genes, (CDKN2a, CDH13, APC, and RASSF1a), which was associated with significantly improved progression-free and overall survival. Four of the 19 patients who received anticancer therapies immediately after epigenetic therapy had major objective responses.

"Combined epigenetic therapy with low-dose azacitidine and entinostat results in objective, durable responses in patients with solid tumors and defines a blood based biomarker that correlates with clinical benefit," the authors write.

One study author disclosed financial ties to Syndax, which develops epigenetic therapy. Two of the study authors disclosed financial ties to MDxHealth, and several authors hold a patent licensed to MDxHealth, a molecular diagnostic company with patented DNA methylation biomarkers.

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