Early Camizestrant Is Favored Upon ESR1 Mutation Emergence in Breast Cancer

In an interview with CancerNetwork®, Erica L. Mayer, MD, MPH, discussed the rationale for switching to camizestrant (Etcamah) at the time of subclinical ESR1 mutation emergence rather than reserving oral selective estrogen receptor degrader (SERD) therapy for documented radiographic progression in patients with hormone receptor (HR)–positive, HER2-negative advanced breast cancer. Mayer is the director of Breast Cancer Clinical Research and an institute physician at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School.

When the phase 3 SERENA-6 trial (NCT04964934) was designed, post-progression options were limited; today, clinicians can deploy oral SERDs such as elacestrant (Orserdu) or combinations targeting PIK3CA mutations after radiographic progression.¹ Mayer explained that medical oncologists generally prefer to use highly effective agents earlier rather than hold them in reserve, and she pointed to the SERENA-6 findings, including prolonged progression-free survival, improved PFS2, delayed time to chemotherapy, and preserved quality of life, as supporting an early switch. The FDA approved camizestrant on September 4, 2026, for patients with emerging ESR1 mutations detected during first-line aromatase inhibitor plus CDK4/6 inhibitor therapy.²

Transcript:

It speaks to a lot of the conversation that has gone on in the medical oncology world since the SERENA-6 results were first presented in 2025. In general, and this goes for all medical oncology, when we have a good drug that is highly effective, we generally want to deploy it earlier. We do not tend to keep our good tools in our back pocket for later because we know cancers acquire additional resistance over time and can become more challenging to treat. If we have an effective strategy, we don’t want to delay; we want to use it.

The notable findings from SERENA-6, including not only the significant prolongation in progression-free survival but also some of the other key end points, such as improvement in PFS2, a significant improvement in time to chemotherapy, and a very dramatic improvement in the delay in deterioration of quality of life, all speak to the efficacy of making the early switch to the SERD when the resistance mutation has emerged. By making that early switch, we are delaying or preventing the development of additional resistance mutations that could make the cancer harder to treat in the future. There is a very strong rationale to deploy the best tool as early as you can, when it is the appropriate time to use it, as opposed to delaying or not using it until a later time of disease progression.

Additionally, we know that the camizestrant-based regimen in SERENA-6 is extremely well tolerated. We know that patients who received this regimen had less pain, fatigue, and nausea compared with those who did not receive this regimen and remained on their prior therapy. We want these things for patients. We want them to feel better. We want to delay subclinical progression of disease, and so that is also a strong rationale for why making the switch early to the appropriate tool makes clinical sense.

References

1. Bidard FC, Mayer EL, Park YH, et al. First-line (1L) camizestrant (CAMI) for emergent ESR1 mutations (ESR1m) in advanced breast cancer: final progression-free survival 2 from the phase III SERENA-6 trial. J Clin Oncol. 2026;44(suppl 17):LBA1007. doi:10.1200/JCO.2026.44.17_suppl.LBA1007
2. FDA grants accelerated approval to a new breast cancer treatment. News release. FDA. September 4, 2026. Accessed September 9, 2026. https://tinyurl.com/ym8hw67u