Abstract PD10-04: 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 (ESR1

Abstract Background In SERENA-6, switching to CAMI from AI while continuing CDK4/6i at emergence of ESR1m during first-line therapy in pts with HR+/HER2− ABC significantly improved PFS, was well tolerated, and reduced the risk of deterioration in quality of life vs AI + CDK4/6i. Photopsia was the most commonly reported non-hematological adverse event (AE) (20% CAMI + CDK4/6i vs 8% AI + CDK4/6i). Previous data suggest that visual effects with CAMI + CDK4/6i are mild, of short duration and have no/minimal impact on activities of daily living. We report a detailed analysis of pt-reported visual functioning and further details of visual effects in SERENA-6. Methods AE incidence, grade (NCI-CTCAE v5.0), and time to onset were recorded for the visual effects group term (photopsia, vision blurred, visual impairment, diplopia, photophobia, and visual perseveration). Ophthalmologic assessments, including fundoscopy, slit lamp, visual acuity, and optical coherence tomography, were conducted at baseline, as clinically indicated, and at end of treatment. Pt-reported visual functioning (measured by the National Eye Institute 25-Item Visual Function Questionnaire [NEI-25]) was an exploratory endpoint. The NEI-25 was completed at baseline, every 6 months thereafter, and at treatment discontinuation. Data cutoff: Nov 28, 2024. Results Overall, 49 (32%) pts in the CAMI + CDK4/6i arm and 25 (16.1%) pts in the AI + CDK4/6i arm reported a visual effect AE. Among the 49 pts in the CAMI + CDK4/6i arm, visual effects were G1 in 44 (90%) pts, G2 in 4 (8%) pts, and G3 (photopsia) in 1 (2%) pt. Median time to first report of a visual effect AE was 8 days with CAMI + CDK4/6i and 23 days with AI + CDK4/6i. Visual effects did not lead to treatment discontinuation in either arm. Clinically significant ophthalmological findings were rare (<6%), unilateral, non-progressive, and occurred at similar frequencies in both arms. Visual effects did not lead to changes in visual acuity and structural evaluations indicated preserved retinal and optic nerve integrity. Mean scores in NEI-25 items, including ability to drive, perform near/distant activities and role function, at Weeks 26 and 52 were similar to baseline scores and comparable between arms (Table). NEI-25 items not reported here show a similar pattern. Conclusions Pt-reported visual functioning with CAMI + CDK4/6i was similar to the AI + CDK4/6i arm. 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. Citation Format: A. Brufsky, F. Bidard, E. L. Mayer, Y. Park, W. Janni, C. Ma, M. Cristofanilli, G. Bianchini, H. Iwata, P. A. Fasching, Z. Nowecki, J. Pascual, S. Chen, L. Moreau, M. Ruiz, A. Shai, N. Karadurmus, K. Jung, Y. Kikawa, R. Baird, C. Arizmendi, I. Leddin, S. McClain, C. Huang Bartlett, N. Turner. 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) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD10-04.