FDA Approves Camizestrant Plus CDK4/6 Inhibitor for ESR1-Mutant Breast Cancer

The FDA granted accelerated approval to camizestrant (Etcamah) in combination with a CDK4/6 inhibitor (abemaciclib [Verzenio], palbociclib [Ibrance], or ribociclib [Kisqali]) for adult patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer who develop an ESR1-mutation during aromatase inhibitor and CDK4/6 inhibitor therapy.¹

The approval is based on the phase 3 SERENA-6 trial (NCT04964934) which compared switching to camizestrant plus a CDK4/6 inhibitor versus continuing an aromatase inhibitor plus a CDK4/6 inhibitor after ESR1 mutation detection. The primary results showed a median progression-free survival (PFS) of 16 months versus 9.2 months in the camizestrant vs control arms, respectively (HR, 0.44; 95% CI, 0.31-0.60; P < .00001).^1,2

Updated SERENA-6 results presented at the 2026 ASCO Annual Meeting, at a median follow-up of 23.5 months, showed median PFS of 16.8 months versus 9.2 months, respectively (HR, 0.45; 95% CI, 0.34-0.59; nominal P < .00001).³ A key secondary end point, time to second progression (PFS2), also favored the camizestrant switch, at a median of 25.7 months versus 19.1 months (HR, 0.63; 95% CI, 0.46-0.86; P = .00373).

ESR1 mutations are acquired resistance alterations that can emerge during standard aromatase inhibitor therapy in patients with locally advanced or metastatic breast cancer. To detect these mutations, the FDA also approved the Guardant360 CDx assay as a companion diagnostic to identify patients eligible for the camizestrant regimen.

The SERENA-6 safety profile for camizestrant in combination with palbociclib, ribociclib or abemaciclib was consistent with the established safety profile of each treatment. There were no new safety signals and the number of discontinuations was similarly low in both arms of the trial.

“This combination provides an important new option for the one in three patients with this form of advanced breast cancer whose tumors develop ESR1 mutations before clinical or radiographic disease progression. Today’s approval will enable clinicians to promptly intervene and change therapeutic strategy at an earlier opportunity ahead of disease progression, rather than waiting until the cancer becomes harder to treat, and patient outcomes and quality of life worsen,” Kevin Kalinsky, MD, MS, FASCO, division director of Medical Oncology, Winship Cancer Institute of Emory University and SERENA-6 investigator stated in the news release.⁴

FDA Approves Camizestrant Despite Negative ODAC Vote

The approval follows a bumpy regulatory path. An April 2026 meeting of the FDA's Oncologic Drugs Advisory Committee (ODAC) ended with the committee voting that the SERENA-6 data did not establish a favorable benefit-risk profile for the early-switch strategy, and the agency subsequently extended camizestrant's Prescription Drug User Fee Act action date to review supplementary data.^5,6

SERENA-6 Trial Design

SERENA-6 is a randomized, double-blind, placebo-controlled trial that enrolled 315 adults with estrogen receptor-positive, HER2-negative advanced breast cancer who were receiving an aromatase inhibitor plus a CDK4/6 inhibitor as initial endocrine-based therapy without evidence of progression. Patients had to have an ESR1 mutation in circulating tumor DNA detected centrally using Guardant360 CDx.

Patients were assigned 1:1 to switch to camizestrant 75 mg once daily while continuing their CDK4/6 inhibitor, or to continue their aromatase inhibitor and CDK4/6 inhibitor. Investigator-assessed PFS was the primary end point, with PFS2 as a key secondary end point.

The accelerated approval of camizestrant is eventually contingent upon results from a confirmatory trial.

“I commend both the FDA and the sponsor for their commitment to advancing cancer care and securing this accelerated approval,” Angelo de Claro, MD, director of the FDA’s Oncology Center of Excellence, stated in a news release.¹ “This marks the first FDA approval of a cancer therapy guided by the detection of a resistance mutation in circulating tumor DNA before imaging tests show that the disease is progressing. But additional evidence is needed to confirm clinical benefit.”

References

1. FDA grants accelerated approval to a new breast cancer treatment. U.S. Food and Drug Administration. Published September 4, 2026. Accessed September 5, 2026. https://tinyurl.com/4rhw6vub

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 (1L) camizestrant (CAMI) for emergent ESR1 mutations (ESR1m) in advanced breast cancer (ABC): final progression-free survival 2 (PFS2) from the phase III SERENA-6 trial. J Clin Oncol. 2026;44(suppl 17):LBA1007. doi:10.1200/JCO.2026.44.17_suppl.LBA1007

4. Etcamah in combination with a CDK4/6 inhibitor approved in the US for 1st-line advanced HR-positive breast cancer. Published online and accessed September 4, 2026. https://tinyurl.com/cbs6nyer

5. Update on FDA Advisory Committee vote on camizestrant in combination with a CDK4/6 inhibitor for advanced HR-positive breast cancer. Published online April 30, 2026. Access September 5, 2026. https://tinyurl.com/5x2kzce7

6. US FDA decision date extended for SERENA-6 filing of camizestrant to enable review of additional data. Published online May 27, 2026. Accessed September 5, 2026. https://tinyurl.com/3b7xjfws