CHMP Recommends Camizestrant Plus CDK4/6 Inhibitor for ESR1-Mutated HR+ Advanced Breast Cancer

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of camizestrant in combination with a CDK4/6 inhibitor for adult patients with estrogen receptor (ER)–positive, HER2-negative locally advanced or metastatic breast cancer upon detection of an emergent ESR1 mutation and without disease progression during frontline endocrine therapy plus a CDK4/6 inhibitor.¹

The recommendation is based on results from the phase 3 SERENA-6 trial (NCT04964934), which were shared during the 2025 ASCO Annual Meeting and were published simultaneously in The New England Journal of Medicine.^2,3

Findings from a planned interim analysis of SERENA-6 indicated that switching from an aromatase inhibitor (AI) like anastrozole or letrozole to camizestrant, while continuing the same CDK4/6 inhibitor, reduced the risk of disease progression or death by 56% compared with continuing an AI plus CDK4/6 inhibitor.³ The median progression-free survival (PFS) was 16.0 months (95% CI, 12.7-18.2) vs 9.2 months (95% CI, 7.2-9.5) in the respective arms (HR, 0.44; 95% CI, 0.31-0.60; P < .00001). The 12-month PFS rates in these arms were 60.7% vs 33.4%, and the 24-month PFS rates were 29.7% and 5.4%.

“This recommendation represents an important step forward for patients with advanced breast cancer in Europe and a milestone in the adoption of new treatment strategies. Through prompt intervention with the camizestrant combination to treat emergence of resistance before it causes disease progression and deterioration of quality of life, we are able to extend the benefit of first-line treatment and optimise outcomes.”¹
-François-Clément Bidard, MD, PhD

Bidard is a professor of medical oncology at Institut Curie and Versailles University in Paris/Saclay, France, and co-principal investigator for SERENA-6.

What was the design of the SERENA-6 trial that supported the CHMP recommendation?

SERENA-6 was a phase 3, randomized, double-blind, placebo-controlled trial enrolling 315 adult patients with hormone receptor–positive, HER2-negative advanced breast cancer who had received an AI plus a CDK4/6 inhibitor as initial endocrine-based therapy for at least 6 months.² Eligible patients had an emergent ESR1 mutation detected in circulating tumor DNA with no evidence of disease progression at the time of detection.

Patients underwent ESR1 mutation surveillance using Guardant360 CDx liquid biopsy testing every 2 to 3 months at the time of routine staging scans. Of 3,325 patients screened, 3,256 underwent ESR1 mutation surveillance; 548 had an ESR1 mutation detected, and 315 were ultimately randomized. Among those with a positive result, 51% were positive on their first test, 38% after 2 to 5 tests, and 11% after more than 5 tests.

Patients were randomized 1:1 to camizestrant at 75 mg once daily plus the same CDK4/6 inhibitor and placebo for AI, or to continuing an AI plus CDK4/6 inhibitor and placebo for camizestrant. Stratification factors included visceral vs nonvisceral disease, time of ESR1 mutation detection at first test vs subsequent test, time from initiation of an AI plus CDK4/6 inhibitor to randomization (less than 18 months vs 18 months or more), and CDK4/6 inhibitor received (palbociclib [Ibrance] vs ribociclib [Kisqali] vs abemaciclib [Verzenio]). The primary end point was investigator-assessed PFS per RECIST v1.1. Secondary end points include second PFS (PFS2), overall survival (OS), safety, and patient-reported outcomes (PROs).

In a recent OncLive News Network,⁴ Hope S. Rugo, MD, and Seth Wander, MD, PhD, unpacked the implications of SERENA-6, highlighting the potential benefits of early oral SERD deployment in breast cancer treatment:

What did secondary end point and subgroup data show with camizestrant in SERENA-6?

The PFS benefit in favor of camizestrant was consistent across all prespecified subgroups, including by age, race, region, menopausal status, disease site, time from initiation of AI plus CDK4/6 inhibitor, CDK4/6 inhibitor received, and specific ESR1 mutation type. Notably, patients receiving ribociclib had an HR of 0.27 (95% CI, 0.08-0.77), although the subgroup was small (n = 23 in the AI plus CDK4/6 inhibitor arm).

For the key secondary end point of PFS2, an interim analysis with 54% information fraction showed an HR of 0.52 (95% CI, 0.33-0.81; P = .0038) in favor of camizestrant; this was directionally consistent with the primary PFS result, although this did not cross the prespecified interim significance threshold of P < .0001. A subsequent preplanned analysis demonstrated a statistically significant PFS2 benefit of 25.7 months vs 19.1 months (HR, 0.63; 95% CI, 0.46-0.86; P = .00373).¹ OS data were immature at the initial data cutoff of November 28, 2024, with 39 deaths (12.4%) reported.² OS will continue to be assessed.¹

In a past Rapid Readouts program, Wander reported PROs from SERENA-6.⁵ In a past episode of Two Onc Docs, Karine Tawagi, MD, and Samantha A. Armstrong, MD, discussed key efficacy, safety, and PROs from SERENA-6.⁶

What was the safety profile of camizestrant in combination with CDK4/6 inhibition?

The safety profile of camizestrant in combination with a CDK4/6 inhibitor in SERENA-6 was consistent with the known profiles of each individual agent. Any-grade adverse effects (AEs) occurred in 94% of patients in the camizestrant plus CDK4/6 inhibitor arm (n = 155) vs 87% in the AI plus CDK4/6 inhibitor arm (n = 155); grade 3 or higher AEs were reported in 60% vs 46% of patients, respectively. Serious AEs occurred in 10% vs 12% of patients, and rates of treatment discontinuation due to AEs were very low and comparable between arms.

Among AEs occurring in at least 10% of patients, hematologic toxicity—primarily neutropenia, anemia, and leukopenia—was the most common in both arms. A notable toxicity of special interest in the camizestrant arm was photopsia reported in 20% of patients vs 0% in the control arm. However, photopsia had no or minimal impact on daily activities, was typically brief (lasting ≤1 minute, ≤3 days per week), was reversible, and was not linked with structural changes in the eye or changes in visual acuity. Bradycardia and sinus bradycardia were reported in 8 patients (5.2%) in the camizestrant arm; none were grade 3 or higher, and none required treatment discontinuation. According to AstraZeneca, no new safety concerns were identified in the trial.¹

What are some recent updates with camizestrant?

Regulatory applications for camizestrant in this setting are currently under review in the United States, Japan, and other countries.

On April 30, 2026, the FDA’s Oncologic Drugs Advisory Committee voted 6-3 that switching to camizestrant upon emergence of an ESR1 mutation during treatment with an AI and a CDK4/6 inhibitor ahead of radiographic disease progression did not demonstrate clinically meaningful benefit for the treatment of this population.^7-9 “The data for changing the paradigm just isn’t there. There is a PFS benefit—if there was an OS benefit, I think I would have voted yes, for sure,” Stanley Lipkowitz, MD, PhD, of the National Cancer Institute, said regarding his no vote. “Aside from OS, I don’t see how they can demonstrate [the benefit of] early vs late [treatment] at this point. [However,] I agree that the bar should be high here, because it’s changing fundamentally the way we do business, and I do agree with the FDA’s concern that all the [subsequent] trials will do exactly this, with no evidence that [early treatment switch] is improving outcomes.”

In a recent interview with OncLive, Rena D. Callahan, MD, of David Geffen School of Medicine at UCLA, explained SERENA-6 data could influence practice, especially if this approach is approved by the FDA.¹⁰ “What we don't know is, at the end of the day, are patients going to live longer? We don't have that information. There was an analysis of PFS2, which was difficult to interpret, given that 1 of the treatment arms [consisted of patients who had received] 3 different treatments, and the other arm [consisted of patients who had received] 2 [different treatments]. But [the PFS2 data] provide some rationale to make [treatment] changes based on molecular findings or blood tests.”

References

1. 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 22, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/camizestrant-recommended-for-breast-cancer-in-eu.html
2. Turner NC, Mayer EL, 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. Rugo HS, Wander S. Ways oral SERDs and targeted therapies could continue to reshape ER+ breast cancer management. OncLive.com. January 16, 2026. Accessed May 22, 2026. https://www.onclive.com/view/ways-oral-serds-and-targeted-therapies-could-continue-to-reshape-er-breast-cancer-management
5. Wander S. Patient-reported outcomes from the SERENA-6 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. OncLive.com. November 7, 2025. Accessed May 22, 2026. https://www.onclive.com/view/patient-reported-outcomes-from-the-serena-6-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
6. Tawagi K, Armstrong SA. Two Onc Docs podcast on ASCO 2025 plenary: SERENA-6. OncLive.com. June 24, 2025. Accessed May 22, 2026. https://www.onclive.com/view/asco-2025-plenary-serena-6
7. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. Accessed April 30, 2026. https://www.youtube.com/live/taCx7enN7hk
8. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee. Draft agenda. FDA. Accessed April 30, 2026. https://www.fda.gov/media/192151/download
9. Ryan C. FDA ODAC live updates: committee reviews SERENA-6 data for camizestrant in ESR1-mutated, hormone receptor+ breast cancer. OncLive.com. April 30, 2026. Accessed May 22, 2026. https://www.onclive.com/view/fda-odac-preview-serena-6-data-for-camizestrant-in-esr1-mutated-hormone-receptor-breast-cancer-take-center-stage
10. Wahner A. Long-term data expand the horizon of hormone receptor+ breast cancer therapies: Q&A with Rena D. Callahan, MD. OncLive.com. April 26, 2026. Accessed May 22, 2026. https://www.onclive.com/view/long-term-data-expand-the-horizon-of-hormone-receptor-breast-cancer-therapies