Dr Hurvitz on SERENA-6 and Weighing an Early Switch to Camizestrant in Breast Cancer

“[The QOL and patient-reported outcomes benefit is] the most compelling argument for an early switch based on ctDNA in patients without radiographic progression.”

Sara A. Hurvitz, MD, FACP, senior vice president and director of the Clinical Research Division, the Smith Family Endowed Chair in Women’s Health, and an affiliate investigator in the Translational Science and Therapeutics Division at the Fred Hutchinson Cancer Center; as well as head of the Division of Hematology and Oncology at the University of Washington School of Medicine, discussed the potential clinical implications of the design of and outcomes from the phase 3 SERENA-6 trial (NCT04964934) in light of World Breast Cancer Research Day, which is observed annually on August 18.

SERENA-6 evaluated a circulating tumor DNA (ctDNA)–guided switch to the next-generation oral selective estrogen receptor degrader (SERD) camizestrant plus a CDK4/6 inhibitor in patients with hormone receptor (HR)–positive, HER2-negative advanced breast cancer and an emergent ESR1 mutation. In SERENA-6, patients receiving a first-line aromatase inhibitor plus a CDK4/6 inhibitor underwent serial ctDNA testing, and those who developed an emergent ESR1 mutation without radiographic progression were randomly assigned to switch the aromatase inhibitor to camizestrant and continue the same CDK4/6 inhibitor or continue their aromatase inhibitor–based regimen, Hurvitz explained. The early switch improved chemotherapy- and ADC-free survival, as well as progression-free survival, she noted.

The overall survival (OS) outcomes were not significantly different between the 2 arms, Hurvitz said, though she emphasized that SERENA-6 was not powered to assess OS. However, there is considerable interest in continuing to follow OS data in this trial to see whether a separation between the arms emerges over time, she added.

The trial also evaluated ctDNA dynamics, Hurvitz noted. Patients who switched to camizestrant had a greater drop in detectable ctDNA than those who continued their aromatase inhibitor plus a CDK4/6 inhibitor. Additionally, patients who achieved total ctDNA clearance had better survival. However, ctDNA clearance is a prognostic indicator, and the study did not necessarily prove that camizestrant was required to achieve that clearance, she cautioned.

Describing SERENA-6 as having a complex study design that the field is still grappling with, Hurvitz said quality of life (QOL) and patient-reported outcomes did appear better with camizestrant. In her opinion, that QOL advantage is the most compelling argument for an early, ctDNA-guided switch in patients without radiographic progression.

Hurvitz also said many investigators would have welcomed a crossover design in which control-arm patients who did not switch could be offered camizestrant at the time of radiographic progression. Such a design, she noted, would have made the trial more valuable for understanding whether an early switch itself benefits patients. Even so, she called SERENA-6 a rich source of emerging data and said she looks forward to longer-term follow-up as it continues.