Phase III ctDNA-guided switch to camizestrant + CDK4/6i in HR+/HER2- ABC with emergent ESR1 mutation. PFS HR 0.44; ODAC voted 6-3 against on Apr 30, 2026 — NOT FDA approved.
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Trial slides shared by KOLs at ASCO 2025 LBA4 / NEJM. Click any image to expand. OCR text extracted via AWS Textract.
[Slide 1] Progression-free Survival among All Patients 100 90 83.2 Median 80 No. of Patients Camizestrant Progression-free with Event (%) Survival (95% CI) 70 Percentage of Patients 60.7 mo 60 62.4 Camizestrant 71 (45.2) 16.0 (12.7-18.2) 50 (N=157) Aromatase 40.3 40 Aromatase Inhibitor Inhibitor 100 (63.3) 9.2 (7.2-9.5) 29.7 30 (N=158) 33.4 Adjusted hazard ratio for disease 20 progression or death, 10 13.5 0.44 (95% CI, 0.31-0.60) 5.4 P<0.0001 0 0 3 6 9 12 15 18 21 24 27 30 33 Months since Randomization No. at Risk Camizestrant 157 138 105 82 55 41 26 11 9 7 6 0 Aromatase inhibitor 158 124 73 55 29 17 7 3 1 0 0 0
[Slide 1] SAN ANTONIO BREAST CANCER Switching to camizestrant + CDK4/6i prolongs time to SYMPOSIUM® UT Health AACR progression and time to first subsequent therapy - American Association - Cancer tear Mays Cancer Cester Updated PFS* CAMI + CDK4/6i Al + CDK4/6i Events 90/157 115/158 100 mPFS Switching to camizestrant + CDK4/6i treatment led to (95% CI); mo 16.6 (14.7-19.4) 9.2 (7.2-9.7) 90 a clinically meaningful improvement in PFS compared Hazard ratio (95% CI): 0.46 (0.34-0.62); P<0.00001 80 with continuing Al + CDK4/6i 70 60 PFS (%) A mPFS: 7.4 months 50 40 The time to first subsequent therapy (defined as the time from randomization to receiving a first 30 subsequent therapy, or death) also favored the 20 camizestrant + CDK4/6i arm compared with the Al 10 + CDK4/6i arm; hazard ratio (95% CI): 0.47 0 (0.35-0.62) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 The magnitude of benefit in time to first Patients Time from randomization (months) subsequent therapy was consistent with PFS at risk CAMI + CDK4/6i 157 143 125 109 82 62 39 26 18 11 7 5 5 0 AI + CDK4/6i 158 127 90 72 42 28 17 9 4 1 1 0 0 0 CAMIL camizestrant, mo, months; CI, confidence interval DCO2, data cutoff 2: mPFS, median PFS; TFST, time to first subsequent therapy, RECIST, Response Evaluation Criteria in Solid Tumors, *Second pre-specified data cut DC02: June 30, 2025. At DCO2 58 patients in the camizestrant * CDK4/61 arm and 23 patients in the AI . CDK4/61 arm were still receiving study treatments status detectable at first versus subsequent CIDNA tests, and time from initiation of Al CDK4/6) to randomization There were 68/157 TFST events in the camizestrant CDK4/61 arm and 117/158 in the Al CDK4/61 arm. PFS was defined per RECIST v1.1. The PFS and TFST hazard ratio and 95% CI are estimated using a Cox proportional hazards model stratified by disease site, ESR1m --- [Slide 2] SAN ANTONIO BREAST CANCER SYMPOSIUM® UT Health AACR Conclusions Security American Carver - Mays Cancer Center PFS results at DCO2 were consistent with those at DCO1. Switch to camizestrant with continuation of CDK4/6i at ESR1m emergence and ahead of disease progression showed a clinically meaningful improvement of >7 months compared with continuing Al + CDK4/6i in patients with HR+/HER2- advanced breast cancer Hazard ratios for PFS2, time to first/second subsequent therapy, chemotherapy/ADC-free survival, and GHS/QoL* also favor the camizestrant + CDK4/6i arm Camizestrant + CDK4/6i profoundly reduced ESR1m allele frequency within 8 weeks, whereas it substantially increased for most patients continuing Al + CDK4/6i Overall survival remains immature (22%)+ Camizestrant + CDK4/6i was well-tolerated, consistent with previous findings, and no new safety signals were observed Switching first-line endocrine therapy to camizestrant, with continued CDK4/6i, significantly extends treatment benefit by delaying disease progression, prolonging chemotherapy/ADC- free survival and time to deterioration in quality of life, as well as profoundly and rapidly reducing ESR1m allele frequency "GHS/QoL hazard ratio 0 49 (95% CI, 0.31-077). AI data cutoff, 69 deaths had occurred (34 patients with camizestrant . COK4/61 vs 35 patients with Al CDK4/6L hazard ratio 0.92 [95% CI, 0.57-1.48[). Second pre-specified data cut DCO2: June 30, 2025.
[Slide 1] SERENA-6 study design SERENA-6 Phase III, randomized, double-blind, placebo-controlled study (NCT04964934) Camizestrant (75 mg qd) + Primary endpoint Female/male patients with continuing CDK4/6i ER+/HER2-ABC* + placebo for Al PFS by investigator assessment (RECIST v1.1) All patients that have Stratification factors received AI + CDK4/6i Visceral VS non-visceral Secondary endpoints (palbociclib, ribociclib, or ESR 1m detection at first test VS at a abemaciclib) as initial R 1:1 subsequent test PFS2** endocrine-based therapy for N=315 Time from initiation of AI + CDK4/6i to ABC for at least 6 months randomization: <18 VS ≥18 months OS** Palbociclib VS ribociclib VS abemaciclib ESR1 detected in ctDNA Safety with no evidence of disease Continuing AI (anastrozole/ progression letrozole) + CDK4/6i Patient-reported + placebo for camizestrant outcomes Treatment continued until disease progression, unacceptable toxicity, patient withdrawal or death *Pre- or perimenopausal women, and men received a luteinizing hormone-releasing hormone agonist per clinical guidelines. "Key secondary endpoint OS, overall survival; PFS2, second progression-free survival; qd, once daily dose; R, randomized; RECIST, response evaluation criteria in solid tumors. 2025 ASCO PRESENTED BY: Nicholas Turner, MD, PhD #ASCO25 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] Primary endpoint: Investigator-assessed PFS SERENA-6 Camizestrant + AI + CDK4/6i (N=157) CDK4/6i (N=158) 100 PFS events 71 100 90 Median PFS (95% CI); months 16.0 (12.7-18.2) 9.2 (7.2-9.5) 80 Adjusted HR (95% CI): 0.44 (0.31-0.60); P<0.00001 70 AI + CDK4/6i 60.7% 60 Camizestrant + CDK4/6i PFS (%) 50 40 29.7% 30 33.4% 20 10 5.4% 0 0 3 6 9 12 15 18 21 24 27 30 33 Time from randomization (months) Number of patients at risk Camizestrant + CDK4/6i 157 138 105 82 55 41 26 11 9 7 6 0 AI + CDK4/6i 158 124 73 55 29 17 7 3 1 0 0 0 P-value crossed the threshold for significance (P=0.0001). PFS was defined per RECIST v1.1. HR was estimated using the Cox proportional hazard model adjusted for stratification factors CI, confidence interval; HR, hazard ratio. 2025 ASCO PRESENTED BY: Nicholas Turner, MD, PhD #ASCO25 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.neg org. KNOWLEDGE CONQUERS CANCER --- [Slide 3] Second progression-free survival (PFS2) SERENA-6 Camizestrant + AI + Key secondary endpoint CDK4/6i (N=157) CDK4/6i (N=158) PFS2 events 38 47 Adjusted HR (95% CI): 0.52 (0.33-0.81); P=0.0038 100 [interim analysis threshold P=0.0001] 85.4% 90 Information fraction: 54% 80 70 74.4% 60 PFS2 (%) Camizestrant + CDK4/6i 50 40 30 AI + CDK4/6i 20 10 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Time from randomization (months) Number of patients at risk Camizestrant + CDK4/6i 157 146 120 103 74 55 39 17 12 9 6 1 0 AI + CDK4/6i 158 144 98 78 55 38 25 12 7 5 1 0 0 HR was estimated using the Cox proportional hazard model adjusted for stratification factors Final PFS2 analysis will occur at 158 PFS2 events. 2025 ASCO PRESENTED BY: Nicholas Turner, MD, PhD #ASCO25 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation a property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 4] Adverse events (≥10% of patients) SERENA-6 Camizestrant + CDK4/6i (N=155) Al + CDK4/6i (N=155) Total / Grade ≥3 Grade 1 Grade 2 Grade ≥3 Grade ≥3 Grade 2 Grade 1 Grade ≥3 / Total Any adverse event, 145 (94%) Any adverse event, 135 (87%) Neutropenia 55 45 34 45 Anemia 17 5 5 17 Leukopenia 17 10 3/8 Hematological adverse events Photopsia 20 1 0/8 Non-hematological adverse events Arthralgia 16 / 0 1 17 Fatigue 15 0 1 14 Dry eye 12 0 07 Exposure time-adjusted incidence rates were similar between Nausea 10 / 0 1 14 treatment arms for neutropenia Back pain 10/1 0 10 Diarrhea 9/0 1 11 Headache 8 1 0 13 70 60 50 40 30 20 10 00 10 20 30 40 50 60 70 Patients (%) Photopsia (brief flashes of light in the peripheral vision) did not impact daily activities: If experienced, visual effects had no/minimal impact on daily activities, were typically ≤1 minute, <3 days/week, and reversible. There were no structural changes in the eye and no changes in visual acuity Neutropenia is reported as a group term that includes neutropenia and decreased neutrophil count; anemia is reported as a group term that includes anemia and hemoglobin decreased; leukopenia is reported as a group term that includes leukopenia and white blood cell count decrease Bradycardia and sinus bradycardia were reported in the camizestrant CDK4/61 arm only. in 8 patients (5.2%) and 4 patients (2.6%), respectively No (sinus) bradycardia AEs were grade 23, and none of these events required treatment discontinuation Impact of visual effects was measured using the Visual Symptom Assessment Questionnaire 2025 ASCO PRESENTED BY: Nicholas Turner, MD, PhD #ASCO25 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER
[Slide 1] SERENA-6 study design SERENA-6 Phase III, randomized, double-blind, placebo-controlled study (NCT04964934) Camizestrant (75 mg qd) + Primary endpoint Female/male patients with continuing CDK4/6i + ER+/HER2-ABC* placebo for Al PFS by investigator assessment (RECIST v1.1) All patients that have Stratification factors received AI + CDK4/6i Visceral VS non-visceral Secondary endpoints (palbociclib, ribociclib, or ESR 1m detection at first test VS at a abemaciclib) as initial R 1:1 subsequent test PFS2** endocrine-based therapy for N=315 Time from initiation of Al + CDK4/6i to ABC for at least 6 months randomization: <18 VS ≥18 months OS** Palbociclib VS ribociclib VS abemaciclib ESR 1m detected in ctDNA Safety with no evidence of disease Continuing AI (anastrozole/ progression letrozole) + CDK4/6i Patient-reported + placebo for camizestrant outcomes Treatment continued until disease progression, unacceptable toxicity, patient withdrawal or death *Pre- or permenopausal women, and men received a luteinizing hormone-releasing hormone agonist per clinical guidelines. "Key secondary endpoint OS, overall survival; PFS2, second progression-free survival; qd. once daily dose; R, randomized; RECIST, response evaluation criteria in solid tumors. 2025 ASCO PRESENTED BY: Nicholas Turner, MD, PhD ASCO AMERICAN SOCIETY OF #ASCO25 CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] Primary endpoint: Investigator-assessed PFS SERENA-6 Camizestrant + AI + CDK4/6i (N=157) CDK4/6i (N=158) 100 PFS events 71 100 90 Median PFS (95% CI); months 16.0 (12.7-18.2) 9.2 (7.2-9.5) 80 Adjusted HR (95% CI): 0.44 (0.31-0.60); P<0.00001 70 AI + CDK4/6i 60.7% 60 Camizestrant + CDK4/6i PFS (%) 50 40 29.7% 30 33.4% 20 10 5.4% 0 0 3 6 9 12 15 18 21 24 27 30 33 Time from randomization (months) Number of patients at risk Camizestrant + CDK4/6i 157 138 105 82 55 41 26 11 9 7 6 0 AI + CDK4/6i 158 124 73 55 29 17 7 3 1 0 0 0 P-value crossed the threshold for significance (P=0 0001) PFS was defined per RECIST v1.1. HR was estimated using the Cox proportional hazard model adjusted for stratification factors CI, confidence interval; HR, hazard ratio 2025 ASCO PRESENTED BY: Nicholas Turner, MD. PhD #ASCO25 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER
[Slide 1] MEDICINE KONEW The NEW ENGLAND OF JOURNAL of MEDICINE ORIGINAL ARTICLE f X in x First-Line Camizestrant for Emerging ESR1- Mutated Advanced Breast Cancer Authors: François-Clément Bidard, M.D., Ph.D. ID Erica L. Mayer, M.D., M.P.H. ID , , Yeon Hee Park, M.D., Ph.D., Wolfgang Janni, M.D., Ph.D., Cynthia Ma, M.D., Ph.D., Massimo Cristofanilli, M.D. ID , Giampaolo Bianchini, M.D., +18 , for the SERENA-6 Study Group* * Author Info & Affiliations Published lune 1, 2025 I Copyright © 2025 --- [Slide 2] A Progression-free Survival among All Patients 100 90 83.2 Median 80 No. of Patients Camizestrant Progression-free with Event (%) Survival (95% CI) 70 Percentage of Patients 60.7 mo 60 62.4 Camizestrant 71 (45.2) 16.0 (12.7-18.2) 50 (N=157) Aromatase 40.3 40 Aromatase Inhibitor Inhibitor 100 (63.3) 9.2 (7.2-9.5) 29.7 30 (N=158) 33.4 Adjusted hazard ratio for disease 20 progression or death, 10 13.5 0.44 (95% CI, 0.31-0.60) 0 5.4 P<0.0001 0 3 6 9 12 15 18 21 24 27 30 33 Months since Randomization No. at Risk Camizestrant 157 138 105 82 55 41 26 11 9 7 6 0 Aromatase inhibitor 158 124 73 55 29 17 7 3 1 0 0 0 B Progression-free Survival in Clinically Relevant Subgroups Hazard Ratio for Disease Progression Subgroup Camizestrant Aromatase Inhibitor or Death (95% CI) no. of events/total no. All patients 71/157 100/158 0.44 (0.31-0.60) Age at randomization <65 yr 44/95 67/104 0.51 (0.34-0.74) >65 yr 27/62 33/54 0.35 (0.21-0.59) Race Asian 22/39 25/34 0.60 (0.33-1.07) White 37/97 61/102 0.39 (0.26-0.59) Other 12/21 14/21 0.39 (0.18-0.85) Region Asia 19/40 28/39 0.46 (0.25-0.83) Europe 37/89 54/91 0.41 (0.26-0.62) North America 15/28 18/28 0.57 (0.28-1.13) Menopausal status at randomization Pre- or perimenopausal women and men 14/34 18/31 0.39 (0.19-0.79) Postmenopausal women 57/123 82/127 0.46 (0.32-0.65) Disease site Visceral 32/65 37/64 0.57 (0.35-0.92) Nonvisceral 39/92 63/92 0.38 (0.25-0.56) No. of organs involved 1 25/55 30/51 0.44 (0.26-0.76) 2 21/51 40/59 0.49 (0.28-0.82) >3 25/51 30/48 0.43 (0.25-0.73) Time from initiation of aromatase inhibitor+CDK4/6 inhibitor until randomization <18 mo 28/50 29/46 0.60 (0.35-1.01) >18 mo 43/105 69/110 0.39 (0.26-0.58) CDK4/6 inhibitor maintained at randomization Palbociclib 57/117 78/118 0.45 (0.32-0.64) Ribociclib 4/23 13/23 0.27 (0.08-0.77) Abemaciclib 10/15 9/15 0.63 (0.25-1.59) Time of ESR1 mutation detection First test 36/82 56/79 0.32 (0.20-0.49) Subsequent test 35/75 44/79 0.64 (0.41-0.99) No. of ESR1 mutations Single mutation 61/131 79/126 0.45 (0.32-0.64) Multiple mutation 10/26 21/32 0.45 (0.20-0.93) Type of ESR1 mutation D538G 29/70 52/82 0.34 (0.21-0.53) Y537S 24/61 46/60 0.29 (0.17-0.47) Y537N 13/29 18/25 0.44 (0.21-0.90) 0.06 0.13 0.25 0.50 1.00 2.00 Camizestrant Aromatase Inhibitor Better Better
[Slide 1] Q = AstraZeneca Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR- positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 Phase III trial PUBLISHED 26 February 2025 --- [Slide 2] First and only next-generation oral SERD and complete ER antagonist to demonstrate 1st- line benefit in combination with widely approved CDK4/6 inhibitors Positive high-level results from a planned interim analysis of the SERENA-6 Phase III trial showed that AstraZeneca's camizestrant in combination with a cyclin- dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) demonstrated a highly statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS). The trial evaluated switching to the camizestrant combination versus continuing standard- of-care treatment with an aromatase inhibitor (AI) (anastrozole or letrozole) in combination with a CDK4/6 inhibitor in the 1st-line treatment of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumours have an emergent ESR1 mutation. --- [Slide 3] advanced breast cancer whose tumours have an emergent ESR1 mutation. The key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the time of this interim analysis. However, the camizestrant combination demonstrated a trend toward improvement in PFS2. The trial will continue as planned to further assess key secondary endpoints. SERENA-6 is the first global, double-blind, registrational Phase III trial to use a circulating tumour DNA (ctDNA)- guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression. The novel trial design used ctDNA monitoring at the time of routine tumour scan visits to identify patients for early signs of endocrine resistance and the emergence of ESR1 mutations. Following detection of an ESR1 mutation without disease progression, the endocrine therapy of patients was switched to camizestrant from ongoing treatment with an --- [Slide 4] Step one: ESR1m detection phase Step two: double-blind, randomized treatment phase 15 standard of care treatment with Al (letrozole or anastrozole) - CDK4/6i (palbociclib or abemaciclib) Study treatment* Screening (n = 3000) ESR1m surveillance Second screening Key inclusion criteria Every 2-3 treatment Key inclusion criteria cycles Switch to camizestrant Histologically confirmed ESRim detected by central (75 mg OD) HR+/HER2- ABC Tumor imaging per standard testing of ctDNA Maintain same CDK4/61 Received 26 months of 1L Al of care Evaluable disease Add placebo for Al (letrozole or anastrozole) Centrally tested plasma No evidence of disease plus CDK4/6i (palbociclib or ctDNA for ESR1 status progression by investigator abemaciclib) therapy for assessment ABC with no evidence of Randomization® 1:1 n * 300 disease progression ECOG PS of 0 or 1 ECOG PS of 0 or 1 Adequate organ and marrow function No prior exposure to Continue Al camizestrant, fulvestrant or ESR1m Maintain same CDK4/6i an investigational endocrine therapy (in any setting) Add placebo for Negative Positive camizestrant Discontinuation upon disease progression
Highest-engagement tweets about this trial, ranked by KOL discussant count (replies + quote-tweets). Replies in green, quote-tweets in blue. Wall Street, stock-promo, and non-substantive replies excluded.
The @NEJM has published SERENA-6 data ahead of @ASCO #ASCO25 plenary. Cami joins other SERDS (elacestrant, imlunestrant, vepdegestrant) with activity in ESR1mut BC Key questions to think about ahead of session: https://t.co/iROohAJG5k
1. Intensive ctDNA screening of 10 patients to find 1 who might qualify for 'switching' based on ESR1mut. Worthwhile? 2. Does switching among asymptomatic patients with no radiological progression make sense when drug c
3. Is this fundamentally different than switching treatment based on small upticks in serum tumor markers, without overt progression? 4. Adds to data from EMBER-3 that SERD + CDK46i looks to be effective. Is 2nd line C
https://t.co/3KHSlaUZ60 https://t.co/JAAh1SWJKz
What we really need to 👀, what we patients want to see, is ⏰ to PFS2 & ultimately OS. For some an oral SERD may be more tolerable than an AI (I’m a patient who has been on AIs/CERANs/injected SERDs so I’m allowed to use
Lead time bias can’t be ruled out and pts in the control arm should have been offered the intervention at clinical progression. This design is like seeing people falling off a cliff and only offering the benefit to some,
+4
The #SERENA6 phase 3 trial is positive: a switch to camizestrant + CDK4/6i (vs continuation of AI + CDK4/6i) upon emergence of ESR1 mutations led to a significant improvement in PFS. PFS2 and OS, which will be key to interpret the results, remain immature. https://t.co/hm2o9EhT5t
Now how to get your oncologist to do the test?
In my opinion PFS2 and OS are the important points.
The new way of thinking regarding the evaluation of the response. The New Era in Oncology ☺️.
Será que é clinicamente significante? E o custo justificará o tamanho do benefício? @xai gerou esta imagem de Marte pensando no tamanho do benefício #Grok3 https://t.co/cWhWiHdT8h
+4
SERENA-6: ctDNA guided approach to switching from AI to camizestrant upon development of ESR1m in combo with cdk4/6i demonstrates improvement in PFS! PFS2 + OS immature Could be a paradigm shift + could introduce ctDNA monitoring into practice https://t.co/eP2RKeK6QE
But need to see overall PFS and OS in SERENA6 (ESR1m in ctDNA - early switch to cami + CDK4/6) vs. switching to/sequential elacestrant at progression on CDK4/6 + NSAI and + ESR1m?
Estamos nos preparados pra usar o ctDNA ? Qual custo da medicação e o tamanho do benefício? https://t.co/IC3G0I260A
+4
Metastatic HR+ #BreastCancer #SABCS highlights w/ @hoperugo: ✅ #AMBRE ✅ #MONALEESA ✅ #VIKTORIA1 ✅ #SERENA6 ✅ #evERA ✅ #EMBER3 ✅ #ASCENT07 Full Discussion: ⭐️ https://t.co/13d2vTlika ⭐️ “Oncology Brothers” podcast #OncTwitter #bcsm @OncoAlert @OncUpdates https://t.co/GD
+4
As anticipated, SERENA-6 creates a lot of questions. PFS-2 is immature and crossover was not allowed; given PFS on postMonarch & EMBER-3 combo, it is unclear to me that early switch based on molecular disease is practice changing. #ASCO25 https://t.co/dnUqTLZbGp
SERENA-6 is the first registrational Phase III trial to use circulating tumor DNA (ctDNA)-guided therapy switching to address emergent endocrine resistance in HR+/HER2- advanced breast cancer. Patients on 1L aromatase inhibitor (AI) plus CDK4/6 inhibitor were monitored every 2-3 months for ESR1 mutations; upon ctDNA detection (without clinical or radiologic progression), patients were randomized to switch to camizestrant (next-generation oral SERD) plus their ongoing CDK4/6 inhibitor or continue the AI plus CDK4/6 inhibitor. The trial demonstrated a 56% reduction in risk of disease progression or death and substantially preserved quality of life. Camizestrant has received FDA Breakthrough Therapy Designation; however, the FDA's Oncologic Drugs Advisory Committee (ODAC) voted 6-3 against recognizing clinically meaningful benefit on April 30, 2026, citing immature OS data, PFS2 acceptability concerns, and cardiac AEs in combination with ribociclib. The FDA's final action on NDA 220359 is pending.
Camizestrant received FDA Breakthrough Therapy Designation based on SERENA-6 results. NDA 220359 was filed for camizestrant in combination with a CDK4/6 inhibitor for HR+/HER2- advanced breast cancer with emergent ESR1 mutation. On April 30, 2026, the FDA's Oncologic Drugs Advisory Committee voted 6-3 AGAINST recognizing clinically meaningful benefit, citing immature OS, PFS-2 acceptability concerns, and ribociclib-combination cardiac risk. The trial is NOT FDA approved. ODAC votes are advisory and non-binding; FDA's final action is pending.
ODAC vote: ODAC vote: 6-3 against (April 30, 2026); FDA decision pending
Population: Adults with HR+/HER2- locally advanced or metastatic breast cancer on 1L AI (anastrozole or letrozole) plus CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) for ≥6 months without progression, with ESR1 mutation detected in ctDNA during routine monitoring.
Interventions: Camizestrant (oral, once daily) + ongoing CDK4/6 inhibitor versus continued AI (anastrozole or letrozole) + same CDK4/6 inhibitor. Switch triggered by ctDNA-detected ESR1 mutation prior to clinical progression.
Endpoints: Primary: investigator-assessed PFS per RECIST 1.1. Key secondary: OS, time to second disease progression (PFS2). Exploratory: time to deterioration in QoL (EORTC QLQ-C30).
Median PFS was 16.0 months (95% CI 12.7-18.2) with camizestrant versus 9.2 months (95% CI 7.2-9.5) with continued AI (HR 0.44; 95% CI 0.31-0.60; p<0.00001) — a 56% reduction in risk of progression or death. 12-month PFS rates: 60.7% vs 33.4%; 24-month PFS rates: 29.7% vs 5.4%. PFS2 HR 0.52 (95% CI 0.33-0.81; p=0.0038), with 12-month PFS2 rates of 85.4% vs 74.4%. Time to deterioration in QoL: 23.0 vs 6.4 months (HR 0.53; p<0.001). OS data immature at primary analysis.
Grade 3+ AEs from all causes: 60% (camizestrant) vs 46% (AI), majority hematologic from CDK4/6i: neutropenia (45% vs 34%), leukopenia (10% vs 3%). Photopsia (reversible peripheral light flashes) reported with camizestrant — no structural eye changes or impact on daily activities. Treatment discontinuation rates very low: 1% camizestrant, 2% AI; CDK4/6i discontinuation 1% in both arms.
Paolo Tarantino summarized the topline: “The #SERENA6 phase 3 trial is positive: a switch to camizestrant + CDK4/6i (vs continuation of AI + CDK4/6i) upon emergence of ESR1 mutations led to a significant improvement in PFS,” while flagging that “PFS2 and OS, which will be key to interpret the results, remain immature.” Sara Tolaney framed the practical implication: “Could be a paradigm shift + could introduce ctDNA monitoring into practice.” Stephanie Graff dissented sharply: “As anticipated, SERENA-6 creates a lot of questions. PFS-2 is immature and crossover was not allowed; given PFS on postMonarch & EMBER-3 combo, it is unclear to me that early switch based on molecular disease is practice changing.” Harold Burstein noted that “@NEJM has published SERENA-6 data ahead of @ASCO #ASCO25 plenary” and that camizestrant “joins other SERDS (elacestrant, imlunestrant, vepdegestrant) with activity in ESR1mut BC.” The April 2026 ODAC reversal sharpened these open questions — the field is now waiting on the FDA’s final NDA decision before the PFS-only signal becomes practice.
