FDA ODAC Live Updates: Committee Reviews SERENA-6 Data for Camizestrant in ESR1-Mutated, Hormone Receptor+ Breast Cancer

The first session of the April 30, 2026, meeting of the FDA’s Oncologic Drugs Advisory Committee (ODAC) is underway, with the group reviewing data from the phase 3 SERENA-6 trial (NCT04964934) for camizestrant in combination with a CDK4/6 inhibitor for patients with hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer upon emergence of ESR1 mutation during first-line endocrine-based therapy.

Follow here for live updates over the course of the morning session, and check back for OncLive’s full story on ODAC’s vote immediately after the decision.

9:00 AM: The meeting opened with FDA remarks, where representatives from the regulatory agency outlined background for ESR1 mutations in hormone receptor–positive breast cancer; overviewed the design of SERENA-6 and challenges with the study; and considerations for the committee.

Among the challenges outlined, the FDA highlighted that the clinical meaningfulness of a PFS improvement measured from the time of ESR1 mutation detection—rather than radiographic progression—is uncertain. The regulatory agency also explained that time to second progression (PFS2) is not typically used in regulatory decision-making, since it does not isolate the effect of the experimental drug. The FDA pointed out heterogeneity in the choice and timing of subsequent therapies; selection of therapy based on availability and local standards of care; and varying assessments of second disease progression.

The opening hour of the meeting also featured public comments before representatives from AstraZeneca began their presentations.

9:45 AM: During AstraZeneca’s presentations, Massimo Cristofanilli, MD, FACP, of Weill-Cornell Medicine and NY Presbyterian, presented on the background of ESR1 mutations in hormone receptor–positive breast cancer and unmet needs for this patient population, underscoring that switching therapy at the emergence of this alteration could allow patients to remain on an endocrine therapy– and CDK4/6 inhibitor–based first-line therapy for a longer duration.

After AstraZeneca outlined the efficacy, safety, and patient-reported outcome data from the study, Kevin Kalinsky, MD, MS, FASCO, of Emory University School of Medicine, provided clinical perspectives on these data, highlighting that this switch could prolong time to chemotherapy or antibody-drug conjugate treatment, along with the ease of implementation.

10:30am: In further presentations from the FDA, the regulatory agency agreed that the study met its PFS primary end point; however, it was argued that it is uncertain if PFS2 data were clinically meaningful, since switching the camizestrant in the experimental arm was initiated at the time of the detection of an ESR1 mutation. Given the design of SERENA-6, the FDA communicated to AstraZeneca that PFS2 would not be acceptable as an efficacy end point to support potential approval. Additionally, they highlighted that overall survival data remain immature and may not reach statistical significance. They also acknowledged the potential for cardiac adverse effects (AEs) with camizestrant, particularly when combined with ribociclib.

11:25 AM: Discussions and questions from the committee for the FDA and AstraZeneca are ongoing. The panel is leaving no stone unturned ahead of the upcoming vote.

11:40 AM: The committee is preparing to vote on the question.

11:55 AM: The FDA’s ODAC 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 patients with hormone receptor–positive, HER2-negative metastatic breast cancer.

Read OncLive’s full story on the decision.

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The FDA’s Oncologic Drugs Advisory Committee (ODAC) will convene on Thursday, April 30, 2026, to discuss data for a pair of regulatory submissions in the breast cancer and prostate cancer paradigms.¹

In the first half of the meeting, the committee will focus on data from the phase 3 SERENA-6 trial (NCT04964934) supporting a new drug application (NDA) seeking the approval of camizestrant in combination with a CDK4/6 inhibitor (palbociclib [Ibrance], ribociclib [Kisqali], or abemaciclib [Verzenio]) for the treatment of adult patients with hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer upon emergence of ESR1 mutation during first-line endocrine-based therapy, based on the results of an FDA-approved test.

“ESR1 mutations are quite rare when patients initially begin therapy, but after they have been on first-line therapy in the metastatic setting, [which includes] an aromatase inhibitor plus a CDK4/6 inhibitor, the rate of ESR1 mutations tends to go up significantly. This is thought to be one of the main reasons that patients develop resistance to their regimen,” Erica L. Mayer, MD, MPH, said in a prior interview with OncLive^®.² “The [thought process] in SERENA-6 was that if one could detect this molecular progression prior to the eventual development of clinical progression, then early intervention with an effective therapy to target the ESR1 mutation may help prevent or delay eventual progression and improve outcomes for patients.”

Mayer is director of the Breast Cancer Clinical Research at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School in Boston, Massachusetts.

Before ODAC weighs in on the SERENA-6 data, catch up on the key question the committee will address, along with the previously reported data that have emerged from the trial.

Stick with OncLive throughout the day on Thursday for live coverage of the meeting and a full breakdown of ODAC’s ultimate vote and its implications for camizestrant in this advanced hormone receptor–positive breast cancer setting.

What question will ODAC address regarding data with camizestrant from SERENA-6 in hormone receptor–positive, HER2-negative, ESR1-mutated advanced breast cancer?

After the morning’s presentations from the FDA and AstraZeneca, the ODAC will vote on the following question:^1,3

“Based on the results of SERENA-6, has clinically meaningful benefit for camizestrant been demonstrated for the treatment of patients with hormone receptor–positive/HER2-negative metastatic breast cancer with a tumor ESR1 mutation detected [during aromatase inhibitor] and CDK4/6 inhibitor treatment, prior to radiographic progression?”

What key data from SERENA-6 have previously been presented?

Initial findings presented at the 2025 ASCO Annual Meeting showed that patients who switched to camizestrant plus CDK4/6 inhibition (n = 157) experienced a median progression-free survival (PFS) of 16.0 months (95% CI, 12.7-18.2) per investigator assessment compared with 9.2 months (95% CI, 7.2-9.5) for patients who continued treatment with an aromatase inhibitor plus CDK4/6 inhibition (n = 158; HR, 0.44; 95% CI, 0.31-0.60; P < .00001).⁴ Camizestrant plus CDK4/6 inhibition elicited 12- and 24-month PFS rates of 60.7% and 29.7%, respectively, compared with respective rates of 33.4% and 5.4% for continued aromatase inhibition plus CDK4/6 inhibition.

“We have known that ESR1 mutations are adaptive resistance mechanisms that happen after [treatment with] an aromatase inhibitor,” Kevin Kalinsky, MD, MS, FASCO, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University and professor and director in the Division of Medical Oncology of the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta, Georgia, said in an interview with OncLive^® following the presentation of the ASCO 2025 data.⁵ “In these patients in SERENA-6 who had not had radiographic progression, [we saw] that early switching [to camizestrant plus CDK4/6 inhibition] improved PFS.”

Updated efficacy data were shared during the 2025 San Antonio Breast Cancer Symposium and demonstrated that the median PFS was 16.6 months (95% CI, 14.7-19.4) in the camizestrant arm vs 9.2 months (95% CI, 7.2-9.7) in the control arm (HR, 0.46; 95% CI, 0.34-0.62; P < .00001).⁶

At the 2025 ESMO Congress, data from patient-reported outcome (PRO) analysesdemonstrated that the switch to camizestrant plus CDK4/6 inhibition led to improvements in time to deterioration (TTD) and reduced the risk of clinically meaningful deterioration in patient-reported cancer symptoms and functioning.⁷

PRO findings from ESMO 2025 showed that the median TTD regarding pain was 16.6 months (95% CI, 8.3-not calculable [NC]) for camizestrant plus CDK4/6 inhibition vs 6.5 months (95% CI, 2.7-13.8) with continued aromatase inhibition plus CDK4/6 inhibition (adjusted HR, 0.57; 95% CI, 0.37-0.86). The median TTD for fatigue was not reached (NR; 95% CI, 13.8 months-NC) vs 13.8 months (95% CI, 6.5-NC), respectively (adjusted HR, 0.75; 95% CI, 0.46-1.24). The median TTD regarding shortness of breath was NR (95% CI, 21.3 months-NC) for camizestrant plus CDK4/6 inhibition vs 16.8 months (95% CI, 10.1-NC) for aromatase inhibition plus CDK4/6 inhibition (adjusted HR, 0.52; 95% CI, 0.28-0.93).

Notably, final data on time to second progression (PFS2) will be presented in an oral presentation at the 2026 ASCO Annual Meeting during a session on June 2.⁸

How was the SERENA-6 study designed?

SERENA-6 was a double-blind, randomized study that enrolled patients at least 18 years of age with histologically confirmed estrogen receptor–positive/HER2-negative breast cancer whose disease was locoregionally recurrent or metastatic and not amenable to curative-intent resection or radiation.⁹ Patients needed to be receiving active treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor with or without luteinizing hormone-releasing hormone therapy as initial treatment in the advanced setting. An ESR1 mutation detected via central circulating tumor DNA testing was required. Patients also needed to have an ECOG performance status of 0 or 1, along with adequate organ function.

Patients with emergent ESR1 mutations were randomly assigned to receive camizestrant in combination with the same CDK4/6 inhibitor they were previously receiving and an aromatase inhibitor placebo; or a camizestrant placebo in combination with the same CDK4/6 inhibitor and an aromatase inhibitor. In the experimental arm, camizestrant was administered orally at 75 mg per day.

Along with the primary end point of investigator-assessed PFS per RECIST 1.1 criteria, secondary end points included PFS2, overall survival, chemotherapy-free survival, objective response rate, clinical benefit rate at 24 weeks, quality of life, and pharmacokinetics.

What safety data have been reported from SERENA-6?

Updated safety data presented at SABCS 2025 were consistent with earlier findings.⁶ Results showed that the most common any-grade adverse effects (AEs) reported in at least 10% of patients included neutropenia (camizestrant arm, 32%; control arm, 25%), decreased neutrophil count (28%; 21%), anemia (21%; 21%), decreased white blood cell count (11%; 7%), photopsia (21%; 8%), arthralgia (19%; 19%), fatigue (16%; 16%), back pain (12%; 11%), dry eye (12%; 7%), nausea (10%; 15%), diarrhea (10%; 13%), and headache (9%; 14%).

Two patients (1%) in the camizestrant arm discontinued the agent due to AEs, although no additional patients discontinued the treatment between the first and second data cutoff. Four patients (3%) discontinued an aromatase inhibitor due to AEs, with 1 additional patient discontinuing between the first and second data cutoff.

References

1. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee. Draft agenda. FDA. Accessed April 29, 2026. https://www.fda.gov/media/192151/download
2. Flaherty C. SERENA-6 introduces potential new paradigm of early ESR1 mutation detection to delay progression in HR+ breast cancer. OncLive.com. June 9, 2025. Accessed April 29, 2026. https://www.onclive.com/view/serena-6-introduces-potential-new-paradigm-of-early-esr1-mutation-detection-to-delay-progression-in-hr-breast-cancer
3. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee. Draft questions. FDA. Accessed April 29, 2026. https://www.fda.gov/media/192153/download
4. 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
5. Kalinsky K. Dr Kalinsky on efficacy data from SERENA-6 in ER+/HER2– advanced breast cancer. OncLive.com. June 10, 2025. Accessed April 29, 2026. https://www.onclive.com/view/dr-kalinsky-on-efficacy-data-from-serena-6-in-er-her2-advanced-breast-cancer
6. 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.
7. Mayer EL, Bidard F-C, Park YH, et al. 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. Ann Oncol. 2025;36(suppl 2):S379. doi:10.1016/j.annonc.2025.08.910
8. 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
9. Phase III study to assess AZD9833+ CDK4/​6 inhibitor in HR+/​HER2-MBC with detectable ESR1m before progression (SERENA-6). ClinicalTrials.gov. Updated April 21, 2026. Accessed April 29, 2026. https://clinicaltrials.gov/study/NCT04964934