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< 2 wks to #ASCO25, here is a📝 of 🔑abstracts for general onc that could guide our SoC! - #ATOMIC - #MATTERHORN -...
Metastatic HR+ #BreastCancer #SABCS highlights w/ @hoperugo: ✅ #AMBRE ✅ #MONALEESA ✅ #VIKTORIA1 ✅...
Presented at #ASCO25: In patients with advanced breast cancer, switching to camizestrant with a CDK4/6 inhibitor after ESR1-mutation detection (and before disease progression) led...
The @NEJM has published SERENA-6 data ahead of @ASCO #ASCO25 plenary. Cami joins other SERDS (elacestrant, imlunestrant, vepdegestrant) with activity in ESR1mut...
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 +...
Thematic take on @ASCO breast cancer abstracts: 1. Move 'em up. DB09, ASCENT-04, SERENA-6 are really just trials of using agents earlier in the course of advanced...
#SABCS2025 Francois-Clement Bidard presents updated Serena-6 data. PFS2 and time to ADC/Chemo better with early switch, ctDNA mESR1 fraction decreased. Remaining question is early vs...
#ASCO25. @drteplinsky highlights from phase 3 SERENA-6 trial that found switching to tx w camizestrant if an ESR1 mutation is detected during first-line treatment can help...
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...
Dr. Nicholas Turner presents SERENA-6, Camizestrant + CDK4/6 inhibitor for the treatment of emergent ESR1 mutations during 1L endocrine-tx and ahead of disease progression in pts with HR+/HER2–...
SERENA-6 is a Phase III, global, double-blind, randomized trial evaluating camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), in combination with a CDK4/6 inhibitor versus continuation of aromatase inhibitor plus CDK4/6 inhibitor in patients with HR+/HER2- advanced breast cancer whose tumors develop an emergent ESR1 mutation during first-line therapy. SERENA-6 is the first registrational trial to use circulating tumor DNA (ctDNA)-guided therapy to detect endocrine resistance before clinical progression and direct a preemptive treatment switch.
Phase III, global, double-blind, randomized trial (NCT04964934). Patients on 1L AI + CDK4/6 inhibitor for at least 6 months underwent ctDNA monitoring every 2-3 months for ESR1 mutations. Upon ESR1 mutation detection (without clinical/radiological progression), patients were randomized to switch to camizestrant + same CDK4/6 inhibitor or continue AI + CDK4/6 inhibitor. Stratified by time of ESR1 detection and time from AI + CDK4/6i initiation to randomization. 315 patients randomized from 3,256 screened.
Adults with HR+/HER2- locally advanced or metastatic breast cancer receiving first-line AI (anastrozole or letrozole) in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) for at least 6 months with no disease progression. ESR1 mutation detected in ctDNA during routine monitoring. 315 patients randomized (approximately 1:1).
Camizestrant (oral, once daily) in combination with the patient's ongoing CDK4/6 inhibitor versus continuation of aromatase inhibitor (anastrozole or letrozole) with the same CDK4/6 inhibitor. Treatment switch triggered by ctDNA-detected ESR1 mutation, prior to clinical progression.
Primary endpoint: investigator-assessed PFS per RECIST 1.1. Key secondary endpoints: overall survival (OS) and time to second disease progression (PFS2). Exploratory endpoints: time to deterioration in global health status/quality of life (EORTC QLQ-C30), pain, and other PROs.
SERENA-6 demonstrated a highly significant PFS benefit for the ctDNA-guided switch to camizestrant. 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 the risk of disease progression or death. The 12-month PFS rates were 60.7% versus 33.4%. The 24-month PFS rates were 29.7% versus 5.4%. PFS benefit was consistent across all CDK4/6 inhibitors and clinically relevant subgroups, including type and timing of ESR1 mutation detection.
Overall survival data were immature at the time of analysis. PFS2, a key secondary endpoint, showed an encouraging trend: PFS2 HR was 0.52 (95% CI: 0.33-0.81; p=0.0038), with 12-month PFS2 rates of 85.4% versus 74.4%. Time to deterioration in quality of life was substantially delayed: median 23.0 months versus 6.4 months (HR 0.53; p<0.001).
The safety profile of camizestrant was consistent with the known profiles of each component drug. Grade 3+ AEs from all causes occurred in 60% of camizestrant patients versus 46% in the AI arm, with the majority being hematological events associated with CDK4/6 inhibitors: neutropenia (45% vs. 34%), leukopenia (10% vs. 3%), and anemia (5% vs. 5%). Photopsia (brief peripheral flashes of light) was reported with camizestrant but was reversible, with no structural eye changes or impact on daily activities. Treatment discontinuation rates were very low: 1% discontinued camizestrant, 2% discontinued the AI, and CDK4/6 inhibitor discontinuation was 1% in both arms.
SERENA-6 introduces a new treatment paradigm: ctDNA-guided preemptive therapy switching before clinical progression. By detecting ESR1 resistance mutations early and switching to camizestrant, patients gained nearly 7 months of additional PFS and maintained quality of life for 17 months longer. Key questions include the feasibility and cost of routine ctDNA monitoring in clinical practice, whether this approach will be adopted broadly or remain niche, and whether the SERENA-4 trial (first-line all-comers) may obviate the need for monitoring. The ODAC meeting on April 30, 2026, will review the camizestrant NDA, which has received Breakthrough Therapy Designation.
