Entinostat plus exemestane for hormone receptor-positive advanced breast cancer: long-term overall survival results from the EOC103A3101 randomized controlled trial.

In 30 seconds

This randomized controlled trial assessed long-term overall survival with entinostat plus exemestane versus placebo plus exemestane in 354 patients with hormone receptor-positive, HER2-negative advanced breast cancer that had recurred or progressed after endocrine therapy. After a median follow-up of 31.8 months, median overall survival was 38.6 months with entinostat and 29.2 months with placebo (hazard ratio 0.83, 95% CI 0.62-1.10, P = 0.184). The difference was numerical and not statistically significant; analyses adjusting for subsequent therapies and a per-protocol sensitivity analysis suggested greater benefit.

Key findings

• Median overall survival was 38.6 months (95% CI: 29.6-44.0) with entinostat-exemestane versus 29.2 months (95% CI: 22.5-41.6) with placebo-exemestane (HR 0.83, 95% CI: 0.62-1.10, P = 0.184).
• Median time to post-discontinuation chemotherapy was 11.7 versus 6.8 months, and chemotherapy-free survival was 9.3 versus 5.6 months; both comparisons had P < 0.05.
• Grade ≥3 treatment-emergent adverse events occurred in 65.5% of patients receiving entinostat-exemestane, with no new safety signals reported.

Why it matters

The trial provides longer-term survival and treatment-course data for an endocrine-based combination in advanced disease after endocrine therapy failure. Although the primary overall-survival comparison was not statistically significant, the numerical difference and longer intervals before chemotherapy may inform interpretation of the regimen’s potential benefits alongside its substantial rate of severe treatment-emergent adverse events.

What to keep in mind

The overall-survival comparison was not statistically significant, and the reported greater benefit in adjusted and per-protocol analyses is less definitive than the randomized primary comparison.