For women with ER-positive advanced breast cancer whose tumors develop ESR1 mutations during first-line therapy, the question of whether switching treatments carries tolerable side effects is clinically decisive. Visual disturbances have been a known concern with next-generation selective estrogen receptor degraders (SERDs), and understanding their real-world burden matters enormously for treatment adherence and quality of life.
The SERENA-6 trial — a double-blind, placebo-controlled Phase III study enrolling 315 patients — randomized individuals with circulating tumor DNA-detected ESR1 mutations but without radiological progression to either switch to camizestrant combined with a CDK4/6 inhibitor or continue their aromatase inhibitor plus CDK4/6 inhibitor regimen. Visual adverse events occurred in roughly 32% of the camizestrant arm versus 16% in the control arm. Critically, 90% of these events were Grade 1 in severity, none prompted treatment discontinuation, and ophthalmological assessments detected no changes in visual acuity or ocular structure. Patient-reported visual disturbances emerged as early as week two but resolved after treatment cessation, with the majority lasting under one minute and causing minimal or no functional bother.
This safety profile deserves careful contextualization. Camizestrant belongs to the oral SERD class, which has faced scrutiny over photopsia and other visual phenomena — side effects also observed, though less frequently, with earlier agents like elacestrant. What distinguishes these findings is the use of ctDNA-guided early switching before radiological progression, a strategy gaining traction as a way to preempt resistance. The fact that visual functioning scores during treatment remained comparable to baseline and between arms suggests that objective impairment is minimal even when subjective symptoms are reported. The exploratory nature of the patient-reported outcome analyses and the relatively short follow-up window are meaningful limitations. Nonetheless, the data are reassuring for clinicians and patients weighing whether to act early on ESR1 mutation emergence — a potentially paradigm-shifting therapeutic window this trial is designed to validate.