Considering the Oral SERD and PROTAC Toxicity Profiles

Oral SERDs and PROTACs demonstrate favorable safety profiles with well-tolerated, low-grade toxicities that distinguish them from traditional chemotherapy approaches. Common adverse effects include photopsia with camizestrant, bradycardia with both camizestrant and giredestrant, low-grade diarrhea with imlunestrant, and nausea with elacestrant. These toxicities generally do not require significant dose modifications or treatment discontinuations, maintaining treatment adherence and quality of life for patients.

The differentiated toxicity profiles may influence treatment selection when multiple oral SERDs become available, similar to current decision-making with 3 approved CDK4/6 inhibitors or multiple antibody-drug conjugates. Clinicians can consider patient-specific factors such as existing comorbidities, concurrent medications, and individual tolerance when selecting among available options. Regulatory requirements may include cardiac monitoring for bradycardia or ophthalmologic assessments for visual toxicities, potentially influencing practical implementation.

Combination approvals and accessibility may ultimately drive treatment selection decisions beyond individual toxicity considerations. The high potency and improved pharmacokinetic profiles of these agents compared with fulvestrant, combined with their activity in ESR1-mutant tumors, position them as significant advances in breast cancer treatment. As the field moves toward combination strategies, the favorable tolerability profiles support their integration with other targeted therapies to enhance efficacy while maintaining manageable safety profiles.