camizestrant (AZD9833) / AstraZeneca - LARVOL DELTA

SERENA-6 Trial Validates Molecular-Guided Therapy Switch to Camizestrant (AJMC) - "There were significantly fewer PFS events in the camizestrant cohort vs the aromatase inhibitor cohort (90 vs 115), with the median PFS being 16.6 months (95% CI, 14.7-19.4) vs 9.2 months (95% CI, 7.2-9.7), for a 54% reduced risk of death (HR, 0.46; 95% CI, 0.34-0.62; P < .00001). At 2 years, the PFS rate was 32.2% vs 14.3%, respectively....Overall, after 8 weeks (C3D1), the median (IQR) change from baseline in ESR1 mutation allele frequency via ctDNA was a 100% reduction in the camizestrant cohort but a 66.7% increase (–67.9% to 465.0%) in the aromatase inhibitor arm."

P3 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Development of an ultra-sensitive droplet digital PCR test for monitoring ESR1 variants in liquid biopsies (SABCS 2025) - "Recent interim results from the landmark SERENA-6 Phase III trial demonstrated the potential clinical utility of ctDNA-guided treatment switching, where median progression-free survival was 16.0 months in the camizestrant group versus 9.2 months in the aromatase-inhibitor group when treatment was switched based on ESR1 mutation detection... We have successfully developed a highly sensitive and specific ddPCR test for the detection of multiple ESR1 variants in plasma. The assay performed as designed and meets the analytical requirements required for further clinical development. The achieved sensitivity of 0.025-0.1% with as little as 10 ng of cfDNA positions this ddPCR assay as a potentially valuable tool for liquid biopsy monitoring applications in breast cancer."

Biopsy • Liquid biopsy • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • ER

Current and future use of oral selective estrogen receptor degraders (SERDs) in the management of ER-positive (ER+), HER2-negative (HER2-neg) metastatic breast cancer (mBC): A survey of 20 breast cancer research leaders (RLs) (SABCS 2025) - "Background: The Jan 2023 approval of elacestrant (E) for patients with ER+ HER2-neg mBC and an ESR1 mutation (ESR1mut) with disease progression (PD) on endocrine therapy introduced new considerations for biomarker-guided decision-making. RLs have rapidly incorporated E into the management of progressive ER+ HER2-neg ESR1mut mBC, but the decision to employ this agent appears to be heavily influenced by the global disease burden and the duration of benefit from first-line treatment. Most RLs consider the newly approved imlunestrant largely equivalent to E, and all would also consider its use in combination with abemaciclib in certain situations. Many fewer would use camizestrant for patients found to have an ESR1mut without clinical PD, but an important and significant minority believe this option should be available to select patients."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Visual functioning and characterization of visual effects from SERENA-6, a Phase 3 study of switch to camizestrant (CAMI) from aromatase inhibitor (AI) while continuing CDK4/6 inhibitor (CDK4/6i) at emergence of ESR1 mutations (ESR1m) during first-line therapy for patients (pts) with HR+/HER2− advanced breast cancer (ABC) (SABCS 2025) - "Visual effects reported with CAMI + CDK4/6i were mostly low grade and occurred early in treatment. Together with the clinical efficacy and well-tolerated safety profile of CAMI + CDK4/6i, these data support this combination as a potential new treatment strategy for pts with HR+/HER2− ABC and emergent ESR1m during first-line AI + CDK4/6i."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Staying Ahead of Resistance: ctDNA-Guided Camizestrant Switching in HR+ Breast Cancer (SERENA-6) [WITHDRAWN] (SABCS 2025) - P3 | "Preemptive replacement of the AI with camizestrant upon molecular progression more than doubled median PFS, extended quality-adjusted survival, and deferred progression by targeting ESR1-mutant clones. These results support a new paradigm of personalized endocrine therapy: intervening at the first molecular sign of resistance to prolong endocrine benefit and delay chemotherapy."

Circulating tumor DNA • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Phase 1/2a trial of new generation PARP1-selective inhibitor saruparib + next generation selective ER degrader (SERD) camizestrant in patients (pts) with advanced/relapsed ER+/HER2-negative or low (HER2−) breast cancer (PETRA Module 6) (SABCS 2025) - P1/2, P3 | "Pts could receive prior CDK4/6 inhibitors or fulvestrant, but not oral SERDs. Saruparib + camizestrant was well tolerated with no new safety signals versus prior monotherapy studies of each drug. PK of saruparib in combination with camizestrant was consistent with monotherapy data. Preliminary efficacy of the combination was promising and compared favorably with camizestrant monotherapy."

Clinical • Metastases • P1/2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • ER • HER-2 • PALB2

Updated results and an exploratory analysis of ESR1m circulating tumor DNA (ctDNA) dynamics from SERENA-6, a phase 3 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1 mutations (ESR1m) during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2- advanced breast cancer (ABC) (SABCS 2025) - "Methods SERENA-6, a randomized, double-blind, phase 3 trial, enrolled pts with HR+/HER2- ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (palbociclib/ribociclib/abemaciclib). No new safety signals were observed. These results further support an early switch to CAMI + CDK4/6i during 1L therapy to delay disease progression."

Circulating tumor DNA • Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

The use of oral selective estrogen receptor degraders (SERDs) by community-based general medical oncologists (GMOs) in ER-positive (ER+), HER2-negative (HER2-neg) metastatic breast cancer (mBC): A clinician survey of practice patterns and practical challenges (SABCS 2025) - "The 1/2023 approval of elacestrant (E) for patients with mBC and an ESR1 mutation (ESR1mut) whose disease progresses on endocrine therapy (ET) introduced new treatment considerations into a clinical situation which already had multiple approved therapeutic options...Regarding select other oral SERDs (imlunestrant, camizestrant, giredestrant), 46% of GMOs believe data are not sufficient to determine comparative efficacy...In terms of novel SERDs, many GMOs consider the newly approved imlunestrant equivalent to E and would consider its use with abemaciclib in certain circumstances. While GMOs are generally familiar with the key datasets, they are also highly motivated to learn more. GMOs have rapidly incorporated E into the management of progressive ER+ HER2-neg ESR1mut mBC. Similarities and differences in practice patterns were observed between GMOs and breast cancer research leaders (data available separately) for a number of clinical situations surveyed."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

MODULE 3: Evolving Up-Front Treatment Paradigm for HR-Positive, HER2-Negative Metastatic Breast Cancer (mBC) (SABCS 2025) - "Sponsored by Genentech, a member of the Roche Group, Eli Lilly and Stemline Therapeutics Inc. Optimal approach to and timing of the assessment of relevant biomarkers for patients with HR-positive mBC; increasing relevance of biomarker evaluation in the up-front setting Long-term follow-up from pivotal clinical trials and other relevant research efforts, such as the RIGHT Choice and ABIGAIL trials, evaluating CDK4/6 inhibitors for HR-positive, HER2-negative mBC; factors affecting the selection of a CDK4/6 inhibitor and an endocrine partner Key findings from the Phase III INAVO120 study evaluating inavolisib in combination with palbociclib and fulvestrant as first-line therapy for patients with HR-positive, HER2-negative mBC with a PIK3CA mutation whose disease had progressed during or within 12 months of adjuvant endocrine therapy FDA approval of inavolisib/palbociclib/fulvestrant and clinical role in the treatment of newly diagnosed HR-positive, HER2-negative mBC with a..."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Phase III study: saruparib + camizestrant vs CDK4/6i regimens in HR+/HER2– ABC with BRCA/PALB2 mutations (EvoPAR-Breast01) (ABC8 2025) - No abstract available

P3 data • Oncology • BRCA • CDK4 • HER-2 • PALB2

A randomized phase III study of first-line saruparib (AZD5305) plus camizestrant vs CDK4/6i plus physician's choice endocrine therapy or CDK4/6i plus camizestrant in patients with HR+/HER2− advanced breast cancer with BRCA1/BRCA2/PALB2 mutations (EvoPAR-Breast01) (DGHO 2025) - P3 | "Participants will be randomized 2:2:1 to receive saruparib plus camizestrant, physician's choice CDK4/6i (abemaciclib, ribociclib, or palbociclib) plus physician's choice ET (fulvestrant, letrozole, anastrozole, or exemestane), or physician's choice CDK4/6i plus camizestrant, respectively. Overall survival (OS) is a secondary endpoint. Approximately 500 participants will be randomized."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • CDK4 • HER-2 • HRD • PALB2

Camizestrant: Regulatory decision for ESR1m HR+/HER2-negative advanced breast cancer (based on SERENA-6 trial) in H1 2026 (AstraZeneca) - Q3 2025 Results

Approval • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology

Efficacy and safety of treatments in HR+HER2- advanced breast cancer after cyclin-dependent kinase 4/6 inhibitors progression: A network meta-analysis and scoping review (ESMO 2025) - "The camizestrant (HR=0.49, 95% CI: 0.32–0.76), ribociclib plus ET (HR=0.57, 95% CI: 0.39–0.84), capivasertib plus ET (HR=0.59, 95% CI: 0.48–0.72), elacestrant (HR=0.70, 95% CI: 0.55–0.89), and abemaciclib plus ET (HR=0.73, 95% CI: 0.57–0.94) showed superior PFS compared to ET monotherapy. Camizestrant, ribociclib plus ET, and capivasertib plus ET demonstrated a significantly better PFS compared with amcenestrant or palbociclib plus ET. ADCs including trastuzumab deruxtecan (T-DXd) (PFS HR=0.59, ORR OR=3.53), sacituzumab govitecan (SG) (PFS HR=0.63, ORR OR=1.63), and datopotamab deruxtecan (Dato-DXd) (PFS HR=0.63, ORR OR=1.94) demonstrated better efficacy in both PFS and ORR compared with chemotherapy...ADCs were superior to chemotherapy, with T-DXd showing the most favorable outcomes. Further studies are needed to guide treatment selection in specific subgroups."

Metastases • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Patient-reported outcomes (PROs) from the SERENA-6 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1m during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC) (ESMO 2025) - P3 | "NR, not reached. Conclusions Together with the clinical efficacy and manageable safety profile of CAMI + CDK4/6i, the PROs from the SERENA-6 trial support this combination as a potential new treatment strategy to optimise and improve outcomes in patients with HR+/HER2– ABC and emergence of ESR1 m, ahead of disease progression, during 1L AI + CDK4/6i."

Clinical • Metastases • Patient reported outcomes • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Patient-reported outcomes in the SERENA-6 trial of camizestrant plus CDK4/6 inhibitor in patients with advanced breast cancer and emergent ESR1 mutations during first-line endocrine-based therapy. (PubMed, Ann Oncol) - "Together with the clinical efficacy and manageable safety profile of camizestrant-CDK4/6i, and reduced risk of GHS/QoL deterioration, the PROs from the SERENA-6 trial support switching to this combination as a potential new treatment strategy to optimise and improve outcomes in patients with HR+/HER2- advanced breast cancer and ESR1m emergence, ahead of disease progression, during first-line AI-CDK4/6i."

Journal • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pain • Pulmonary Disease • Solid Tumor • ER • HER-2

Visual symptom questionnaire results from SERENA-6, a phase 3 study of switch to camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) at emergence of ESR1m during first-line (1L) therapy for patients (pts) with HR+/HER2– advanced breast cancer (ABC) (ESMO 2025) - P3 | "Conclusions VE with CAMI + CDK4/6i were typically brief (<1 minute/episode) with no or minimal impact on ADLs. Together with the clinical efficacy and well-tolerated safety profile of CAMI + CDK4/6i, these data support this combination as a potential new treatment strategy for pts with HR+/HER2– ABC and emergent ESR1 m during 1L AI + CDK4/6i."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Vepdegestrant, a PROteolysis Targeting Chimera (PROTAC) estrogen receptor (ER) degrader, induces greater ER degradation and antitumor activity relative to selective ER degraders (SERDs) in preclinical ER+ breast cancer models (AACR-NCI-EORTC 2025) - "Here, we report preclinical ER degradation and antitumor activity of vepdegestrant compared with FDA-approved (fulvestrant and elacestrant) and investigational oral SERDs (giredestrant, camizestrant, amcenestrant, and imlunestrant). Our results indicate that vepdegestrant induces greater maximal ER degradation than investigational oral SERDs, elacestrant, or fulvestrant in WT ER+ breast cancer cell lines. Vepdegestrant also demonstrated greater TGI and ER degradation in vivo compared with fulvestrant in a WT ER+ breast cancer CDX model."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Patient-reported outcomes in the SERENA-6 trial of camizestrant plus CDK4/6 inhibitor in patients with advanced breast cancer and emergent ESR1 mutations during first-line endocrine-based therapy (ScienceDirect, Ann Oncol) - "Switching to camizestrant-CDK4/6i delayed TTD and reduced the risk of deterioration in patient-reported cancer symptoms (pain [hazard ratio 0.57; 95% CI 0.37–0.86], fatigue [0.75; 0.46–1.24], shortness of breath/dyspnoea [0.52; 0.28–0.93], breast symptoms [0.59; 0.28–1.24] and arm symptoms [0.69; 0.34–1.39]) and functioning (physical [0.74; 0.44–1.24], role (0.73; 0.48–1.10] and emotional [0.51; 0.29–0.87]) compared with AI-CDK4/6i."

Patient reported outcomes • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Patient-reported outcomes in the SERENA-6 trial of camizestrant plus CDK4/6 inhibitor in patients with advanced breast cancer and emergent ESR1 mutations during first-line endocrine-based therapy (ScienceDirect, Ann Oncol) - "Switching to camizestrant-CDK4/6i delayed TTD and reduced the risk of deterioration in patient-reported cancer symptoms (pain [hazard ratio 0.57; 95% CI 0.37–0.86], fatigue [0.75; 0.46–1.24], shortness of breath/dyspnoea [0.52; 0.28–0.93], breast symptoms [0.59; 0.28–1.24] and arm symptoms [0.69; 0.34–1.39]) and functioning (physical [0.74; 0.44–1.24], role (0.73; 0.48–1.10] and emotional [0.51; 0.29–0.87]) compared with AI-CDK4/6i."

Patient reported outcomes • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=396 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Nov 2025 ➔ Dec 2026

Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Patient reported data supports SERENA-6 treatment approach to optimize and improve outcomes for patients with advanced breast cancer (Eurekalert) - "Mayer will report findings that the SERENA-6 treatment approach significantly reduced the risk of deterioration of global health status/quality of life compared to staying on aromatase inhibitor and CDK4/6 inhibitor. Further, switching to camizestrant with continuation of CDK4/6 inhibitor consistently delayed time to deterioration in a spectrum of patient-reported cancer symptoms, as well as in daily patient functioning."

Patient reported outcomes • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Hydrolysis of O-, N-, and N+-glucuronide metabolites in human feces. (PubMed, Drug Metab Dispos) - "In this study, the stability of 5 representative O-, N-, and N+-glucuronides (ifenprodil O-glucuronide, valsartan N-glucuronide, candesartan N-glucuronide, camizestrant N-glucuronide, and clomipramine N+-glucuronide) was evaluated in pooled human feces in the presence or absence of β-glucuronidase inhibitors and in aqueous solutions at various pH levels. SIGNIFICANCE STATEMENT: This study demonstrates the rapid hydrolysis of 5 glucuronides to their parent drugs in human feces. The findings highlight the importance of analyzing early and late fecal pools in human absorption, distribution, metabolism, and excretion for drugs with prominent glucuronides in order to determine the origin of the parent drugs in feces."

Journal

Estimating meaningful change thresholds (MCTs) for selected scales from the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires in the phase 3 SERENA-6 trial in patients with hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ABC). (ASCOQLTY 2025) - "This study aimed to estimate MCTs for selected EORTC quality of life (QoL) 30-item core questionnaire (QLQ-C30) scales and breast cancer-specific module (QLQ-BR23) scales using data from the SERENA-6 study in patients with ABC switching first-line endocrine therapy at emergence of ESR1 mutations ahead of clinical or radiologic progression; patients switched to camizestrant or continued to receive aromatase inhibitor, with CDK4/6 inhibitor maintained... MCTs were determined for the selected EORTC scales for use in the PRO endpoint definition and data interpretation in SERENA-6 and another study with a similar population. Using MCTs estimated from blinded study data provides context-specific thresholds that may accurately reflect a meaningful change in PROs for patients in the targeted study population."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Camizestrant causes reversible pharmacological effects on retinal responses in rats. (PubMed, Transl Oncol) - "The results support a reversible, pharmacological effect of camizestrant on retinal responses in the absence of structural changes and are consistent with clinical findings. These data offer insight into the potential mechanism of the visual effects observed in patients."

Journal • Preclinical • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ophthalmology • Solid Tumor

CADILLAC: Efficacy and Safety of Camizestrant Plus Ribociclib in Patients With Breast Cancer (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: MedSIR

New P2 trial • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor