When to Replace Aromatase Inhibitors With SERDs in ER+/HER2– Advanced mBC

Results from the phase 3 persevERA trial (NCT04546009) showed that the use of first-line giredestrant plus palbociclib (Ibrance) showed a numerical improvement in investigator progression-free survival (IN-PFS) but did not meet statistical significance for patients with estrogen receptor–positive, HER2-negative locally advanced metastatic breast cancer.¹

Mabel Mardones, MD, a medical oncologist from Rocky Mountain Cancer Centers, spoke with CancerNetwork during the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting regarding the results from the trial and what the horizon looks like for replacing aromatase inhibitors with oral selective estrogen degrader receptors (SERDs).

The median IN-PFS was 33.1 months (95% CI, 30.2-38.3) in the giredestrant arm vs 28.2 months (95% CI, 25.0-33.1) in the letrozole plus palbociclib arm (HR, 0.89; 95% CI, 0.76-1.05; P = .1553).

Mardones also referenced the ongoing phase 3 SERENA-4 trial (NCT04711252), which is comparing camizestrant plus palbociclib vs anastrozole plus palbociclib in the aforementioned patient population. She noted she was hopeful for these results so that they could best demonstrate a signal within the population.

Transcript:

This is a very crowded space. There are a lot of companies that are looking at this idea of an oral SERD up front. I do think that to some degree this is disappointing. We did want to see a statistically positive study, but there might have been some issues with regards to power in this study. We do await SERENA-4, which is looking at a very similar patient population. They are looking at camizestrant up front. This was a larger study; in this study that we’re referencing, it’s about 992 patients. The other study is about 1600 patients, so we hope to see a signal there. Ultimately, what we want to know and understand is, is there a group of patients who should have an oral SERD up front? That’s going to be teased out with other studies that are looking at the endocrine-resistant population as well.

References

1. Turner NC, Jhaveri KL, Bardia A, et al. Giredestrant (GIRE) + palbociclib (PALBO) vs letrozole (LET) + PALBO as first-line (1L) therapy in patients (pts) with estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer (ER+, HER2– LA/mBC): Primary analysis of the Phase III persevERA BC trial. J Clin Oncol. 2026;44(suppl 17):LBA1006. doi:10.1200/JCO.2026.44.17_suppl.LBA1006
2. Im SA, Hamilton EP, Cussac AL, et al. SERENA-4: A phase 3 comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease. J Clin Oncol. 2021;39(suppl 15):TPS1101. doi:10.1200/JCO.2021.39.15_suppl.TPS1101