SERENA-6 visual patient-reported outcomes & safety: camizestrant for emerging ESR1 m advanced breast cancer during first-line endocrine-basedtherapy

BACKGROUND: We report ophthalmological assessments, patient-reported visual symptoms/functioning, and characterization of visual effect AEs from the SERENA-6 study. MATERIALS AND METHODS: This double-blind, placebo-controlled phase III study included 315 patients with ER-positive advanced breast cancer receiving first-line aromatase inhibitor (AI)+CDK4/6 inhibitor (CDK4/6i). Patients with emerging ESR1 mutations in ctDNA and no radiological progression were randomized 1:1 to switch to camizestrant+CDK4/6i or continue AI+CDK4/6i. Predefined group term visual effect AEs were graded (NCI-CTCAE v5.0). Ophthalmologic assessments were conducted at baseline, as indicated, and end-of-treatment. Analyses of patient-reported visual effects/functioning were exploratory. RESULTS: Visual effect AEs were reported in 49 (31.6%) patients receiving camizestrant+CDK4/6i and 25 (16.1%) patients receiving AI+CDK4/6i; 90% were grade 1; none led to discontinuation. No changes in visual acuity or ocular structure were observed. Patient-reported visual effects occurred early (by week 2) and were reversible post-treatment. The proportion of patients in the camizestrant+CDK4/6i and AI+CDK4/6i arm reporting short-lived visual effects (<1min) ranged from 60%-67% vs 50%-69%, respectively; visual effects causing no/a low degree of bother: 78%-88% vs 50%-75%, respectively. During treatment, visual functioning was comparable to baseline and between arms. CONCLUSION: If experienced, patient-reported visual effects (including photopsia) with camizestrant+CDK4/6i were short-lived and reversible post-treatment. Visual effect AEs with camizestrant+CDK4/6i were mostly mild and did not require treatment discontinuation or ophthalmologic management. There was no impact on ocular structure, function, or visual acuity; visual effects had little/no impact on daily functioning. These findings support clinical decision-making by further characterizing the visual safety profile of camizestrant in this setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04964934.