Supplements and Featured Publications, 2025 ESMO Congress: Focus on Breast Cancer, Volume 1, Issue 1
Use of camizestrant plus a CDK4/6 inhibitor at the emergence of an ESR1 mutation did not significantly worsen visual symptoms in HR-positive breast cancer.
Switching therapy to camizestrant plus a CDK4/6 inhibitor at the time of emergence of an ESR1 mutation during first-line therapy was associated with low degrees of visual effects that minimally affected quality of life (QOL) in patients with hormone receptor–positive, HER2-negative advanced breast cancer, according to findings from a visual symptom questionnaire collected from patients enrolled in the phase 3 SERENA-6 trial (NCT04964934).1
The findings, which were presented at the 2025 ESMO Congress, showed that at baseline, prior to receiving study treatment, 16% of patients in both the camizestrant plus CDK4/6 inhibitor and the aromatase inhibitor (AI) plus CDK4/6 inhibitor arms reported experiencing a visual effect within the past week. Among patients in the camizestrant arm who experienced a visual effect over the course of the study, 46% reported experiencing this effect by week 2. From there, the rates of visual effects reported in the camizestrant arm remained stable until 4 weeks after treatment discontinuation, where levels reduced to below baseline rates. In the AI arm, the patterns of patient-reported visual effects remained stable over time.
Among patients who completed the Visual Symptom Assessment Questionnaire (VSAQ), visual effects within the past week were reported at the below time points and rates:
Week 2: camizestrant arm, 46%; AI arm, 22%
Week 6: 44%; 18%
Week 24: 42%; 23%
Week 36: 41%; 29%
“Visual effects with camizestrant plus a CDK4/6 inhibitor were typically brief (< 1 minute per episode), occurred mostly in the morning or evening, and were infrequent (occurring ≤ 3 days per week),” lead study author Yeon Hee Park, MD, PhD, and coauthors wrote in a poster of the data. “Patients reported that visual effects caused no or a low degree of bother and had no or minimal impact on activities of daily living.”
Park is a professor of medicine at the Sungkyunkwan University School of Medicine and the director of the Clinical Trial Center at Samsung Medical Center in Seoul, Korea.
Switching patients with hormone receptor–positive/HER2-negative advanced breast cancer who developed an ESR1 mutation to receive camizestrant plus a CDK4/6 inhibitor resulted in a statistically significant improvement in median PFS to 16.0 months (95% CI, 12.7-18.2; n = 157) compared with 9.2 months (95% CI, 7.2-9.5; n = 158) for those continuing an AI plus a CDK4/6 inhibitor (HR, 0.44; 95% CI, 0.31-0.60; P < .00001).
Visual effects experienced by patients receiving camizestrant plus a CDK4/6 inhibitor were typically reported to be brief, lasting less than 1 minute per episode. These effects also occurred mostly in the morning or evening and were infrequent.
Patients reported that the visual effects caused little to no degree of bother and had little to no effect on activities of daily living, as assessed by the VSAQ.
What efficacy findings have been previously reported from SERENA-6?
SERENA-6 investigated the efficacy and safety of switching from an AI to camizestrant—a next generation oral selective estrogen receptor degrader and complete estrogen receptor antagonist—and continuing treatment with a CDK4/6 inhibitor in the frontline setting following the emergence of an ESR1 mutation in circulating tumor DNA in patients with hormone receptor–positive, HER2-negative advanced breast cancer who had no evidence of clinical or radiological disease progression.
Previously reported findings showed that patients who switched to camizestrant had a statistically significant progression-free survival (PFS) improvement vs those who continued with an AI, with a median PFS of 16.0 months (95% CI, 12.7-18.2; n = 157) vs 9.2 months (95% CI, 7.2-9.5; n = 158), respectively (HR, 0.44; 95% CI, 0.31-0.60; P < .00001).2 Additionally, switching to camizestrant was shown to delay time to deterioration in global health status/QOL as measured by the EORTC core quality of life questionnaire; this median was 21.0 months (95% CI, 13.8-not calculated) vs 6.4 months (95% CI, 2.8-14.0) with continuation of an AI (adjusted HR, 0.54; 95% CI, 0.34-0.84).3 Photopsia was reported as the most common nonhematological adverse effect following treatment with camizestrant plus a CDK4/6 inhibitor.1
What was the design of the visual symptom analysis of the SERENA-6 trial?
The measurement of vision-related symptoms and functioning per the VSAQ was a predefined exploratory end point of SERENA-6.
“The VSAQ was selected as the most appropriate patient-reported outcome [PRO] tool to measure these aspects of visual effects based on ophthalmological assessments and patient interviews that were performed in [the phase 1] SERENA-1 [trial (NCT03616587)] and [the phase 2] SERENA-2 [trial (NCT04214288)],” the authors explained.
VSAQ adherence was calculated for each prespecified time point (baseline, week 2, week 6, week 24, every 12 weeks thereafter until treatment discontinuation, the treatment discontinuation visit, and 4 weeks after treatment discontinuation). Patients were considered to have an evaluable questionnaire if they had at least 1 subscale completed.
What were the additional findings from the visual symptom analysis of SERENA-6?
Across both arms of the full SERENA-6 population, 155 patients received at least 1 dose of any study treatment and were followed for PROs. At baseline, 68% of patients in the camizestrant arm and 60% of those in the AI arm completed at least 1 VSAQ subscale. VSAQ completion adherence rates increased after the baseline assessment and were consistent between the 2 arms. The range of VSAQ adherence rates after baseline up to week 36 was 73% to 82% for the camizestrant arm vs 70% to 74% for the AI arm.
Regarding the frequency of visual effects, most patients in both arms reported experiencing these 3 or fewer times in the past week. The rates of patients experiencing visual effects at this frequency were as follows at the below time points:
Baseline: camizestrant arm, 71%; AI arm, 67%
Week 2: 59%; 76%
Week 6: 58%; 61%
Week 24: 58%; 56%
Week 36: 73%; 83%
Homing in on the time of day that visual effects were experienced, these rates across the morning, afternoon, and evening between the 2 respective arms were as follows at the below time points:
Baseline:
Morning: camizestrant arm, 18%; AI arm, 33%
Afternoon: 35%; 47%
Evening: 47%; 53%
Week 2:
Morning: camizestrant arm, 50%; AI arm, 36%
Afternoon: 3%; 44%
Evening: 62%; 36%
Week 6:
Morning: camizestrant arm, 48%; AI arm, 17%
Afternoon: 4%; 39%
Evening: 58%; 44%
Week 24:
Morning: camizestrant arm, 30%; AI arm, 19%
Afternoon: 25%; 44%
Evening: 55%; 44%
Week 36:
Morning: camizestrant arm, 30%; AI arm, 42%
Afternoon: 30%; 42%
Evening: 64%; 33%
Taking a look at the duration of visual effects, overall, most patients reported these events lasting less than 1 minute. The rates of patients who experienced visual effects of this duration were as follows:
Baseline: camizestrant arm, 59%; AI arm, 40%
Week 2: 60%; 60%
Week 6: 67%; 50%
Week 24: 63%; 69%
Week 36: 64%; 58%
Across all time points, most patients who had a visual effect reported that they experienced little to no bother from these effects. Notably, no patients in either arm reported being extremely bothered by visual effects. Little bother from these effects was reported at the following rates:
Baseline: camizestrant arm, 59%; AI arm, 73%
Week 2: 52%; 28%
Week 6: 56%; 50%
Week 24: 50%; 38%
Week 36: 55%; 75%
Additionally, the median effect of these visual toxicities on daily living activities was minimal in both arms; these scores were largely consistent across time points.
“Together with the clinical efficacy and well-tolerated safety profile of camizestrant plus a CDK4/6 inhibitor, these data support this combination as a potential new treatment strategy for patients with hormone receptor–positive/HER2-negative advanced breast cancer and emergent ESR1 mutations during first-line AI plus a CDK4/6 inhibitor,” the authors concluded.
References
Park YH , Bidard FC, Mayer E, et al. 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). Ann Oncol. 2025;36(suppl 2):S423-S424. doi:10.1016/j.annonc.2025.08.951
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
Mayer EL, Bidard FC, Park YH, et al. 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. Ann Oncol. Published online October 20, 2025. doi:10.1016/j.annonc.2025.10.006
