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Oral selective estrogen receptor degraders are effective in the estrogen receptor 1 mutation subgroup of estrogen receptor-positive metastatic breast cancer, according to the results of a new study.

Oral selective estrogen receptor degraders (SERDs) are novel agents used to treat estrogen receptor (ER)-positive metastatic breast cancer resistant to other hormonal agents. Elacestrant and camizestrant have shown significant progression-free survival (PFS) benefits in both the overall population and the estrogen receptor 1 (ESR1) mutation (ESR1mt) subgroup. However, elacestrant is only approved for ESR1mt tumors, and camizestrant demonstrated no benefit in the ESR1 wild-type (ESR1wt) subgroup. 

A study in the Annals of Oncology evaluated whether the PFS benefit in the overall population is driven by the ESR1mt subgroup.

Study Population

Four studies assessing 1290 patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer randomized to receive oral selective estrogen receptor degraders (SERDs) versus a physician’s choice of endocrine therapy were included in the analysis.

Benefits of Oral SERDs vs. Physicians’ Choice of Treatment in Overall and ESR1mt Populations

The main outcomes included hazard ratios and Kaplan–Meier (KM) curves for PFS for the overall ESR1mt and ESR1wt populations. The individual patient data (IPD) pooled analysis of the overall population demonstrated a significant PFS benefit with oral SERDs versus treatment of physician’s choice (TPC) (p<0.001); however, the aggregate meta-analysis showed no significant difference. The IPD pooled analysis of the ESR1mt population showed a significant PFS benefit for oral SERDs vs. TPC (p<0.001), with similar results in the aggregate meta-analysis.

Progression-Free Survival With Oral SERDs vs. Physicians’ Choice of Treatment in ESR1wt Population

The IPD pooled analysis of the ESR1wt population showed no statistically significant PFS benefit for oral SERDs vs. TPC (p=0.543), with similar results in the aggregate meta-analysis, despite the positive results in both the overall and ESR1mt populations.

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Subgroup Analysis Demonstrated Consistent Outcomes

The findings remained consistent in the subgroup analysis. Oral SERDs vs. fulvestrant showed similar outcomes in the trials SERENA-2 and EMERALD to oral SERDs vs. TPC, where PFS benefit was seen in the ESR1mt but not the ESR1wt population. KM subtraction showed no significant PFS difference for amcenestrant in the AMEERA-3 ESR1wt population (p=0.180) when compared to TPC. Elacestrant also revealed no significant difference in PFS in the EMERALD ESR1wt population (p=0.493) when compared to fulvestrant.

In conclusion, the study findings suggest that the PFS benefit with oral SERDs in the overall population is mainly driven by the ESR1mt subgroup.

Source

Wong, N. Z. H., Yap, D. W. T., Ong, R. J. M., Zhao, J. J., Chan, Y. H., Tey, J., Sundar, R., Lim, J., & Dawood, S. (2023). Efficacy of Oral SERDs in the treatment of ER+, HER2 – metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups. Annals of Oncology, S0923-7534(23)04328-4. Advance online publication.  https://doi.org/10.1016/j.annonc.2023.10.122