Jason Mouabbi, Assistant Professor at MD Anderson Cancer Center, shared a post on LinkedIn:
“SABCS25 Recap 3: ELEVATE Trial – defining the next chapter for oral SERD combinations
The phase II ELEVATE trial evaluated elacestrant in combination with targeted agents:
Elacestrant plus everolimus: median PFS 8.3 months
Elacestrant plus abemaciclib: median PFS 14.3 months
Here is my take:
1.Elacestrant plus abemaciclib is particularly compelling
A median PFS exceeding 14 months, independent of ESR1 or PIK3CA status, is impressive, especially considering most patients received this regimen in the second-line setting.
This provides strong validation for sequential CDK4/6 inhibitor use when paired with oral SERDs, provided there is no clear mechanism of CDK4/6 resistance (e.g., RB loss).
While consistent with EMBER3 (imlunestrant + abemaciclib: mPFS 9.4 mo), the ELEVATE results stand out given the more refractory population: ~⅓ had prior fulvestrant and ~20% had primary endocrine resistance, both excluded from EMBER3.
2. Elacestrant plus everolimus shows a meaningful and nuanced signal
This combination demonstrated comparable benefit in ESR1-mutant and ESR1-wild-type disease, a pattern not observed in the evERA trial:
ELA plus EVE: mPFS 8.3 mo (ESR1m) vs 9.0 mo (WT)
GIRE plus EVE: mPFS ~10 mo (ESR1m) vs ~6 mo (WT)
This suggests a potentially broader role for elacestrant when paired with mTOR inhibition especially in the ESR1-WT population.
3. Practical sequencing in ESR1-mutant disease
For patients with ESR1 mutations who experienced a durable response (≥12 months) to first-line ET + CDK4/6 inhibition, I would generally avoid adding everolimus:
EMERALD (single-agent elacestrant): mPFS 8.6 months
ELEVATE (elacestrant + everolimus): mPFS 8.3 months
In this context, the added toxicity of everolimus may not be justified.”
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