Elacestrant Improves Real-World Time to Next Treatment or Treatment Discontinuation in ESR1+ HR+/HER2– Breast Cancer

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Among patients with ESR1-mutant hormone receptor (HR)–positive/HER2–negative advanced breast cancer, time to treatment discontinuation and time to the next treatment outcomes with elacestrant (Orserdu) were comparable to or exceeded progression-free survival (PFS) outcomes observed in the phase 3 EMERALD trial (NCT03778931), according to data from a real-world analysis presented during the 2024 San Antonio Breast Cancer Symposium.¹

Among 742 eligible patients for outcomes analysis on elacestrant (mean age, 63 years), the median real-world time to next treatment (rwTTNT) was 6.43 months (95% CI, 5.60-8.03) and the median real-world time to treatment discontinuation (rwTTD) was 4.60 months (95% CI, 4.03-5.40).

The EMERALD trial demonstrated improved PFS of 3.80 months vs 1.9 months compared with standard of care endocrine therapy.^2,3

In addition, most patients received elacestrant beyond the second line of treatment, and the treatment regimen did not significantly impact the outcomes with the drug. Second-line rwTTNT was 8.80 months and 5.30 months for rwTTD. For patients receiving third-line elacestrant, rwTTNT was 5.90 months (HR, 1.31; 95% CI, 0.88-1.97) and rwTTD was 4.50 months (HR, 1.30; 95% CI, 0.91-1.88). For those receiving fourth line elacestrant, rwTTNT was 6.40 months (HR, 1.25; 95% CI, 0.83-1.87) and rwTTD was 4.60 months (HR, 1.14; 95% CI, 0.78-1.70).

Patients with alterations in the PIKA3CA pathway experienced worse outcomes with elacestrant treatment compared with patients without alterations.

Specifically, patients with PI3K pathway alterations experienced shorter time to next treatment (5.2 vs 8.0 months; HR, 1.62, 95% CI, 1.28-2.05), shorter time to treatment discontinuation (4.0 vs 5.3 months; HR, 1.52, 95% CI, 1.23-1.89), and worse overall survival (HR, 1.86; 95% CI, 1.28-2.72).

“It's important to note that even though patients received [elacestrant] at fourth line and beyond that, there was no difference in outcomes for those patients,” Rinath Jeselsohn, MD, Dana-Farber Cancer Institute, said during the poster presentation. “However, patients with alterations with the PIK3CA in the PI3 kinase pathway did have worse outcomes. And this really underscores the need for precision medicine and also for combination treatments in specific patient subgroups.”

Researchers analyzed real-world data from 756 patients with HR+/HER2– advanced breast cancer who were treated with elacestrant after FDA approval. The study assessed time to treatment discontinuation and time to next treatment as proxies for PFS, as well as overall survival. Patients on the study were required to have at least 28 days of follow-up following the first elacestrant claim to be included in the outcomes analysis. Cox-Regression hazard ratios (HRs) were adjusted for patient age, sex, year of ctDNA result, and line of therapy used.

The most common sites of metastasis were bone (n = 554; 73%), brain (n = 71; 9%), liver (n = 237; 31%), and lung (n = 115; 15%). Most patients had received prior treatment with aromatase inhibitors (n = 683; 90%), fulvestrant (n = 402; 53%), CDK4/6 inhibitors (n = 624; 83%), chemotherapy (n = 312; 41%), alpelisib (n = 79; 10%), trastuzumab deruxtecan (T-DXd; Enhertu; n = 58; 8%), and sacituzumab govitecan (Trodelvy; n = 28; 4%).

GuardantINFORM database was used to identify HR+/HER2- breast cancer patients with ESR1 mutation detected on circulating tumor DNA (ctDNA) within 6 months prior to elacestrant initiation. Oncogenic alterations in AKT1, PTEN, and PIK3CA with an FDA approved targeted therapeutic indication were included as PI3K pathway alterations.

"A real-world analysis of patients with advanced hormone receptor-positive breast cancer with ESR1 mutations identified more than 700 patients treated with elacestrant since the approval with very specific criteria. The time to treatment discontinuation and time to next treatment were overall in the range are slightly higher compared to PFS seen in the EMERALD trial, and most of the patients received elacestrant beyond second line of treatment for metastatic disease,” Jeselsohn concluded.

Reference

1. Lloyd M, Ali A, Weipert C, et al. Impact of prior treatment, ESR1 mutational (ESR1m) landscape, and co-occurring PI3K pathway status on real-world (RW) elacestrant outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2negative advanced breast cancer (aBC). Presented at: San Antonio Breast Cancer Symposium (SABCS); 2024 Dec 10-13; San Antonio, TX. Abstract PS7-05.
2. Bidard FC, Kaklamani V, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. Journal of Clinical Oncology. 2022;40(28):3246-3256. doi:10.1200/JCO.22.00338
3. Bardia A, Cortes J, Bidard FC, et al. Elacestrant in ER+, HER2- Metastatic Breast Cancer with ESR1-Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups. Clin Cancer Res. 2024;30(19):4299-4309. doi:10.1158/1078-0432.CCR-24-1073