The phase 3 SERENA-6 (NCT04964934) trial demonstrated that switching to camizestrant plus a cyclin-dependent kinase (CDK)4/6 inhibitor, guided by the emergence of an ESR1 mutation during first-line aromatase inhibitor (AI) plus CDK4/6 inhibitor treatment, resulted in a statistically significant and clinically meaningful improvement in progression-free survival compared with continuing AI plus a CDK4/6 inhibitor in patients with hormone receptor (HR)-positive/HER2-negative advanced breast cancer (ABC). In addition to the clinical efficacy and tolerability, this treatment approach was associated with a reduced risk of deterioration in global health status and quality of life. This article summarizes additional patient-reported outcomes (PROs) reported from SERENA-6.

PROs were assessed at prespecified timepoints using validated tools, including the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30), the EORTC breast cancer–specific module (QLQ-BR23), and the Patient Global Impression of Treatment Tolerability (PGI-TT). The EORTC QLQ-C30 and EORTC QLQ-BR23 assessments occurred every 4 weeks from randomization to week 12 and then every 8 weeks until second progressive disease or death. Time to deterioration (TTD) in breast symptoms, arm symptoms, pain, physical functioning, and role functioning were predefined secondary endpoints. The data cutoff for analysis was November 28, 2024.

A total of 315 patients were randomized to either switch to camizestrant plus a CDK4/6 inhibitor (n=157) or continue AI plus a CDK4/6 inhibitor (n=158). Camizestrant plus a CDK4/6 inhibitor consistently delayed TTD and reduced the risk of deterioration in cancer symptoms and functioning as assessed by the QLQ-C30 and QLQ-BR23 questionnaires compared with AI plus a CDK4/6 inhibitor. TTD analyses revealed that camizestrant plus a CDK4/6 inhibitor reduced the risk of clinically meaningful deterioration in overall global health status/quality of life and pain. Hazard ratios for physical functioning, role functioning, breast symptoms, and arm symptoms also favored camizestrant plus a CDK4/6 inhibitor. Camizestrant plus a CDK4/6 inhibitor delayed TTD in pain (hazard ratio, 0.57; 95% confidence interval [CI], 0.37-0.86), fatigue (hazard ratio, 0.75; 95% CI, 0.46-1.24), and shortness of breath (hazard ratio, 0.52; 95% CI, 0.28-0.93) compared with AI plus a CDK4/6 inhibitor. Camizestrant plus a CDK4/6 inhibitor also delayed TTD of patient-reported functioning, including the ability to perform everyday physical activities (hazard ratio, 0.74; 95% CI, 0.44-1.24), impact of health on work and daily activities (hazard ratio, 0.73, 95% CI, 0.48-1.10), and feelings of anxiety, depression and irritability (hazard ratio, 0.51; 95% CI, 0.29-0.87) compared with AI plus a CDK4/6 inhibitor.

The SERENA-6 trial demonstrated that switching to camizestrant plus a CDK4/6 inhibitor in patients with HR-positive/HER2-negative ABC and emergent ESR1 mutations during first-line AI plus CDK4/6 inhibitor treatment reduced the risk of deterioration in global health status/quality of life, pain, and other key symptoms, while maintaining a favorable tolerability profile. Combined with its clinical efficacy and manageable safety profile, these PRO findings support camizestrant plus a CDK4/6 inhibitor as a promising treatment strategy to optimize outcomes in patients with an ESR1 mutation, ahead of disease progression, during first-line AI plus CDK4/6 inhibitor therapy.

Source: Mayer E, Bidard FC, Park YH, et al. Patient-reported outcomes (PROs) from the SERENA-6 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1m during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC). Presented at: ESMO Congress 2025. October 20, 2025; Berlin, Germany. Abstract 486 MO.