FDA Extends Decision Date for Camizestrant in HR+ Advanced Breast Cancer With an Emergent ESR1 Mutation

The FDA has extended the Prescription Drug User Fee Act target action date for review of the new drug application (NDA) seeking the approval of camizestrant plus a CDK4/6 inhibitor (palbociclib [Ibrance], ribociclib [Kisqali], or abemaciclib [Verzenio]) for the first-line treatment of patients with hormone receptor–positive, HER2-negative advanced breast cancer whose tumors have an emergent ESR1 mutation.¹

The NDA is supported by findings from the phase 3 SERENA-6 trial (NCT04964934). Data presented at the 2025 ASCO Annual Meeting and simultaneously published in The New England Journal of Medicine showed that among patients with hormone receptor–positive, HER2-negative advanced breast cancer whose tumors developed an emergent ESR1 mutation, those who switched to camizestrant plus a CDK4/6 inhibitor (n = 157) achieved a median progression-free survival (PFS) of 16.0 months (95% CI, 12.7-18.2) per investigator assessment vs 9.2 months (95% CI, 7.2-9.5) in those who continued treatment with an aromatase inhibitor plus a CDK4/6 inhibitor (n = 158; HR, 0.44; 95% CI, 0.31-0.60; P < .00001).^2,3 Additionally, updated data presented at the 2025 San Antonio Breast Cancer Symposium showed a median PFS of 16.6 months (95% CI, 14.7-19.4) with the switch to camizestrant vs 9.2 months (95% CI, 7.2-9.7) with the control regimen (HR, 0.46; 95% CI, 0.34-0.62; P < .00001).⁴

“If [the FDA does] approve it, [this will] end up changing the paradigm of what we do for patients,” Jane L. Meisel, MD, FASCO, stated in an interview with OncLive®. “It would mean we should be presumably checking for ESR1 [mutations] on many of these patients at baseline as they start their treatment for metastatic disease, and then potentially making a switch based on these molecular markers, as opposed to imaging, if [imaging is] saying [the patient is] not ready [for a switch in therapy]. That changes things, and we don’t yet have that option.”

Meisel is a professor and co-director of Breast Medical Oncology in the Department of Hematology and Medical Oncology, as well as a professor in the Department of Gynecology & Obstetrics at the Emory University School of Medicine in Atlanta, Georgia.

What is the regulatory history of the SERENA-6 regimen in the United States?

Notably, in May 2025, the FDA granted breakthrough therapy designation to camizestrant plus a CDK4/6 inhibitor for this patient population based on the SERENA-6 data.¹

However, in April 2026, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 6-3 against the clinically meaningful benefit of switching to camizestrant plus a CDK4/6 inhibitor following the detection of an ESR1 mutation in circulating tumor DNA (ctDNA) before ahead of radiographic disease progression.⁵ Following the ODAC decision, at the request of the FDA, AstraZeneca provided additional data to support the NDA, including ctDNA clearance data associated with long-term efficacy outcomes that will be presented at the 2026 ASCO Annual Meeting.¹

“There were a lot of questions about the trial of whether it would benefit patients to change therapy at the point of molecular progression,” Alexis Ann LeVee, MD, said to OncLive in another interview following the ODAC decision. “One of the big downsides of the trial is the fact that it did not allow crossover. By allowing crossover, it would have allowed us to ask the question: Is receiving the switch in therapy at molecular progression better than receiving that same therapy upon radiographic progression? The OS data are still immature, so we're not able yet to comment on whether switching therapy earlier does improve long-term outcomes for patients. [There is also] a focus on needing PRO measures [and] whether starting [treatment] at the time of molecular progression is clinically relevant for patients. There are still a lot of questions based on that trial. However, in theory, it is an exciting trial, and it makes us wonder whether targeting those resistance mutations earlier would benefit patients. But I think the way, unfortunately, they designed the trial has yet to answer that question.”

LeVee is a breast medical oncologist at UCLA Health in Los Angeles, California.

Sarah Sammons, MD, provided additional context and commentary regarding the SERENA-6 trial design, saying, “The SERENA-6 study is quite controversial, and there are many breast medical oncologists who view the SERENA-6 study as where the field needs to go in terms of intercepting biology and resistance before it’s too late. I am in the camp of medical oncologist who feel that this strategy was worth exploring and that this was successful. I was disappointed in the outcome of the ODAC [meeting]. Any paradigm-shifting trial deserves scrutiny. I tend to be in the camp of that. [However], I think this is a strategy that our patients could benefit from, and I also think our patients are open to getting on top of resistance and not waiting until they have deterioration on scans and feel worse before changing therapy. I hope this outcome does not inhibit future novel trial design in this setting. One of the main controversies is that crossover to the oral selective estrogen receptor degrader [SERD] should have been offered in the control arm. This would have been incredibly hard to achieve. In the phase 3 PADA-1 study [NCT03079011], only [approximately] 68% of patients [in the control arm] ended up crossing over [to the investigational arm]. Given the lackluster performance of oral SERDs post-CDK4/6 inhibition, I suspect, in a modern cohort, that [percentage] would have been lower [in SERENA-6], and that would have been challenging.”

Sammons has most recently served as associate director of the Metastatic Breast Cancer Program and a senior physician at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

What is the global regulatory status of camizestrant based on the SERENA-6 data?

On May 22, 2026, the European Medicines Agency’s Committee for Medicinal Products for Human Use announced that it has recommended the approval of camizestrant plus a CDK4/6 inhibitor in this setting based on the data from SERENA-6 that have been published so far.⁶ Camizestrant is also approved in this setting in Saudi Arabia and the United Arab Emirates.¹

What might the future look like for the use of camizestrant switch therapy in ESR1 mutation–emergent hormone receptor–positive HER2-negative advanced breast cancer?

For additional insights regarding the upcoming ASCO 2026 presentation of additional SERENA-6 data, check out our conference preview article, which breaks down when to tune into the presentation and what findings might be revealed.⁷

“My patients do best on their first-line therapy with a CDK4/6 inhibitor,” Sammons concluded. “That’s when they feel the best. It’s when they are living their lives to the fullest: traveling and working full time. I’m open to anything that can prolong their time on first-line therapy and improve their quality of life. Without a doubt, I think the trial showed success in that respect.”

References

1. US FDA decision date extended for SERENA-6 filing of camizestrant to enable review of additional data. News release. AstraZeneca. May 27, 2026. Accessed May 27, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/us-fda-decision-date-camizestrant-extended.html
2. Turner N, Mayer E, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): phase 3, double-blind ctDNA-guided SERENA-6 trial. J Clin Oncol. 2025;43(suppl 17):LBA4. doi:10.1200/JCO.2025.43.17_suppl.LBA4
3. Bidard FC, Mayer EL, Park YH, et al. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N Engl J Med. 2025;393(6):569-580. doi:10.1056/NEJMoa2502929
4. Bidard FC, Mayer EL, Park YH, et al. Updated results and an exploratory analysis of ESR1m circulating tumor DNA dynamics from SERENA-6, a phase 3 trial of camizestrant + CDK4/6 inhibitor for emergent ESR1m during first-line endocrine-based therapy and ahead of disease progression in patients with HR+/HER2– advanced breast cancer. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract RF7-03.
5. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. Accessed May 27, 2026. https://www.youtube.com/live/taCx7enN7hk
6. Camizestrant in combination with a CDK4/6 inhibitor recommended for approval in the EU by CHMP for 1st-line advanced ER-positive breast cancer. News release. AstraZeneca. May 22, 2026. Accessed May 27, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/camizestrant-recommended-for-breast-cancer-in-eu.html
7. Wahner A. ASCO 2026 HR+ and HER2+ breast cancer preview: read up on the insights to know before you go. OncLive.com. May 6, 2026. Accessed May 27, 2026. https://www.onclive.com/view/asco-2026-breast-cancer-preview-read-up-on-the-insights-to-know-before-you-go