- Design
- Phase 3, randomised, placebo-controlled; long-term OS analysis
- Population
- 354 patients with HR+/HER2− advanced breast cancer after endocrine failure
- Primary outcome
- Overall survival (secondary analysis)
- Effect
- Median 38.6 vs 29.2 months; HR 0.83 (0.62–1.10), P = 0.18
Long-term follow-up of a Chinese phase 3 trial, published in Signal Transduction and Targeted Therapy, reports overall survival for 354 patients with HR-positive, HER2-negative advanced breast cancer after endocrine therapy failure, randomised 2:1 to entinostat, a histone deacetylase inhibitor, or placebo, each with exemestane.
At a median 31.8 months, median overall survival was 38.6 versus 29.2 months (HR 0.83, 0.62–1.10; P = 0.18). Time to chemotherapy and chemotherapy-free survival were longer with entinostat. Grade 3 or worse adverse events occurred in 65.5%. Analyses adjusting for later therapies and per-protocol analyses favoured entinostat more strongly.
The earlier progression-free survival benefit has not been shown to translate into a significant survival gain. Adjusted and per-protocol analyses are hypothesis-generating; the intention-to-treat result is the one to rely on.
In a landscape where CDK4/6 inhibitors are standard, the place of entinostat is uncertain.
- Rely on the intention-to-treat survival result, which was not significant
- Treat analyses adjusted for later therapies as hypothesis-generating
- Weigh the 65.5% rate of grade 3 or worse adverse events against an unproven survival gain
Why it matters
A progression-free survival gain did not carry through to a proven survival benefit.
Don't overread it
Adjusted and per-protocol survival gains cannot substitute for the non-significant primary comparison.
The statistics, in plain English
An HR of 0.83 with an interval from 0.62 to 1.10 fits anything from a 38% reduction to a 10% increase in death rate, so the trial cannot confirm a survival benefit.
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