The SERENA-6 study: PRO data

The SERENA-6 study is a pivotal Phase III trial in hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC), designed to evaluate whether early intervention based on detection of ESR1 mutations can prolong the benefits of first-line treatment. This trial follows promising results from the PADA-1 Phase II trial, which demonstrated that switching endocrine therapy upon early detection of ESR1 mutations in circulating tumor DNA (ctDNA), but before radiologic disease progression, could significantly improve progression-free survival (PFS).

SERENA-6 employs a two-step design. In Step 1, patients who had received at least six months of first-line therapy with an aromatase inhibitor (AI) and a CDK4/6 inhibitor underwent serial ctDNA testing every 2–3 months to detect emerging ESR1 mutations. Over 300 patients with ESR1-mutant ctDNA, but without clinical or radiologic evidence of progression, advanced to Step 2 in which they were randomized to either continue the treatment with an AI and a CDK4/6 inhibitor, or switch to the oral selective estrogen receptor degrader (SERD) camizestrant plus CDK4/6 inhibitor with placebo. 

Primary results of this trial showed that patients who switched early to camizestrant demonstrated a significant and clinically meaningful improvement in PFS compared to those who stayed on the AI-based regimen. At ESMO 2025, Dr Erica Mayer, medical oncologist at the Dana-Farber Cancer Institute in Boston, presented patient-reported outcomes (PRO) of this trial, assessing the impact of the treatment on patient quality of life (QoL). In this video, she discusses the PRO data with Prof François Duhoux,  medical oncologist at Cliniques Universitaires Saint-Luc in Brussels.

PROs were captured using the EORTC QLQ-C30 and BR23 questionnaires. These were collected every four weeks for the first three months and less frequently thereafter. Pre-specified secondary endpoints included pain, fatigue, shortness of breath, and functional status. The analysis revealed that patients who switched to camizestrant experienced a delayed deterioration in global health status by approximately 18 months. Furthermore: patients who switched early exhibited delayed worsening in pain, fatigue, and dyspnea compared to the AI continuation group.

Functionally, “switch patients” reported better role and physical functioning, including activities like walking, working, and engaging in daily tasks. These improvements were sustained over time, with early and progressively widening separation of PRO curves favoring the camizestrant arm. This suggests that subclinical symptoms of disease progression are mitigated by the early switch to a more effective endocrine therapy.

Overall, these findings strongly support the clinical value of detecting ESR1 mutations early and adjusting treatment accordingly. This strategy not only improves PFS but also preserves and enhances patient quality of life, a growing priority for patients and regulators alike in the metastatic setting.