Elacestrant shows promising antitumour activity in early breast cancer

Preoperative treatment with the oral nonsteroidal selective ER degrader elacestrant appears to yield biological and molecular responses in early-stage breast cancer, while having a manageable safety profile, as shown in a phase I trial.

The trial included 22 postmenopausal women with untreated ER-positive/HER2-negative breast cancer (T1c [≥1.5 cm] to T3, N0, locally assessed Ki67 ≥10 percent). These patients received elacestrant at 345 mg daily for 4 weeks.

The primary efficacy endpoint of complete cell cycle arrest, defined as Ki67 ≤2.7 percent, on day 28 occurred in 27.3 percent of patients. Mean Ki67 expression decreased by 52.9 percent (95 percent confidence interval, −67.4 to −32.1) from baseline (p=0.007).

Treatment with elacestrant was also associated with a shift toward a more endocrine-sensitive and less proliferative tumour phenotype based on PAM50-based gene signatures. Specifically, there was an increased expression of immune-response genes (GZMB, CD4, and CD8A) and decreased expression of estrogen-signaling genes (MKI67, ESR1, and AR). Notably, these biological changes occurred regardless of the levels of Ki67 suppression on day 28.

As for safety, frequently reported adverse events were grade 1 anaemia (21.7 percent), hot flushes (8.7 percent), constipation (8.7 percent), and abdominal pain (8.7 percent). A grade 3 cutaneous rash occurred in one patient, leading to treatment discontinuation. No other serious adverse events were documented.