Key Takeaways:
- Imlunestrant monotherapy demonstrated delayed disease progression in patients with ESR1 mutations.
- Imlunestrant combined with abemaciclib significantly delayed progression across all patients, regardless of ESR1 mutation status.
Summary:
SAN ANTONIO — Imlunestrant, either as monotherapy or in combination with abemaciclib, improved progression-free survival (PFS) for certain patients with advanced breast cancer resistant to hormone therapy, according to findings from the phase 3 EMBER-3 trial presented at the San Antonio Breast Cancer Symposium.
The trial evaluated 874 patients with ER-positive, HER2-negative advanced breast cancer who had previously undergone endocrine therapy, with or without CDK 4/6 inhibitors. Participants were randomly assigned to receive imlunestrant monotherapy, standard endocrine therapy (fulvestrant or exemestane), or a combination of imlunestrant and abemaciclib.
Results:
- Imlunestrant Monotherapy:
- Among patients with ESR1 mutations, imlunestrant monotherapy reduced the risk of progression or death by 38% compared to standard endocrine therapy (median PFS: 5.5 vs. 3.8 months; HR = 0.62).
- However, for the overall population, monotherapy did not significantly improve PFS compared to standard therapy (median PFS: 5.6 vs. 5.5 months; HR = 0.87).
- Combination Therapy:
- The combination of imlunestrant and abemaciclib reduced the risk of progression or death by 43% compared to imlunestrant alone (median PFS: 9.4 vs. 5.5 months; HR = 0.57).
- The benefit was consistent across subgroups, including those with or without ESR1 mutations and patients with PI3K pathway mutations.
- Safety Profile:
- Imlunestrant monotherapy was well tolerated, with fatigue and diarrhea reported as the most common side effects.
- The imlunestrant-abemaciclib combination had a higher incidence of grade 3 or greater adverse events, including neutropenia, diarrhea, and fatigue, but fewer injection-related side effects compared to fulvestrant.
Clinical Implications:
Imlunestrant, a next-generation selective estrogen receptor degrader (SERD), offers an all-oral alternative to traditional SERDs like fulvestrant, which require monthly intramuscular injections. Its oral bioavailability and ability to cross the blood-brain barrier make it particularly promising for patients with central nervous system metastases.
“The consistency of results across subgroups and the improved ease of administration make imlunestrant a valuable option for patients with ER-positive, HER2-negative advanced breast cancer,” noted researcher Komal Jhaveri, MD, from Memorial Sloan Kettering Cancer Center.
Perspective:
Kate Lathrop, MD, of UT Health San Antonio, emphasized the importance of having multiple therapeutic options to address individual patient needs, considering factors like toxicity, cost, and sequencing. She highlighted the encouraging PFS benefits observed in the trial, particularly for patients without ESR1 mutations or those resistant to endocrine therapy.
Study Limitations:
While the EMBER-3 trial demonstrated promising results, it did not require prior CDK 4/6 inhibitor treatment for eligibility, unlike similar trials such as postMONARCH and EMERALD. Despite this, two-thirds of participants in the combination therapy group had prior exposure to CDK 4/6 inhibitors, and consistent benefits were observed across the trial population.
Conclusion:
Imlunestrant, either alone or combined with abemaciclib, offers a new all-oral treatment option for patients with ER-positive, HER2-negative advanced breast cancer, providing significant clinical benefits and improved patient convenience. Further regulatory review will determine its place in clinical practice.
