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Switching to camizestrant plus a CDK4/6 inhibitor delayed symptom deterioration and improved QOL in HR+ breast cancer with the emergence of ESR1 mutations.
Switching to camizestrant with continuation of a CDK4/6 inhibitor in patients with hormone receptor–positive/HER2-negative advanced breast cancer and the emergence of an ESR1 mutation during first-line treatment with an aromatase inhibitor (AI) and CDK4/6 inhibitor therapy showed consistent benefit in delaying time to deterioration (TTD) and reducing the risk of clinically meaningful deterioration in patient-reported cancer symptoms and functioning, according to new data from the phase 3 SERENA-6 trial (NCT04964934) presented during the 2025 ESMO Congress.1
Patient-reported outcome (PRO) analyses included the EORTC QLQ-C30, which is oncology specific, and EORTC QLQ-BR23, which is breast cancer specific. With regard to pain, a secondary end point, the median TTD when switching to camizestrant plus CDK4/6 inhibition was 16.6 months (95% CI, 8.3-not calculable [NC]) vs 6.5 months (95% CI, 2.7-13.8) with continued AI plus CDK4/6 inhibition (adjusted HR, 0.57; 95% CI, 0.37-0.86). With regard to fatigue, the median TTD was not reached (NR; 95% CI, 13.8-NC) vs 13.8 months (95% CI, 6.5-NC) in the respective arms (adjusted HR, 0.75; 95% CI, 0.46-1.24). In terms of shortness of breath, the median TTD was NR (95% CI, 21.3-NC) with switch to camizestrant plus CDK4/6 inhibition vs 16.8 months (95% CI, 10.1-NC) with AI plus CDK4/6 inhibition (adjusted HR, 0.52; 95% CI, 0.28-0.93).
“Please note these curves separate early and have a maintained separation, suggesting the early switch to camizestrant may be preventing symptoms related to subclinical cancer progression, including pain, fatigue, and shortness of breath,” Erica Mayer, MD, MPH, said in a presentation of the data. Mayer serves as the director of Breast Cancer Clinical Research in the Breast Oncology Program at Dana-Farber Cancer Institute, in Boston, Massachusetts.
Switching to camizestrant also delayed TTD in the secondary end point of physical functioning, which measures the ability to perform everyday physical activities like walking or carrying groceries. The median TTD with camizestrant switch was 23.0 months (95% CI, 17.4-NC) vs 15.7 months (95% CI, 8.3-NC) without (adjusted HR, 0.74; 95% CI, 0.44-1.24).“Switching to camizestrant delayed TTD for both role functioning and emotional functioning, which is particularly notable in the context of a placebo-controlled trial,” Mayer added. The respective adjusted HRs were 0.73 (95% CI, 0.48-1.10) and 0.51 (95% CI, 0.29-0.87).
The double-blind, placebo-controlled, randomized, phase 3 study enrolled patients with estrogen receptor–positive/HER2-negative advanced breast cancer. All patients had completed at least 6 months of frontline AI plus CDK4/6 inhibitor in the form of palbociclib (Ibrance), ribociclib (Kisqali), or abemaciclib (Verzenio) and were found to have emergence of an ESR1 mutation on serial circulating tumor DNA (ctDNA) in the absence of clinical progression.
Patients (n = 315) were randomly assigned 1:1 to switch to camizestrant at 75 mg once daily with continuation of CDK4/6 inhibitor and the addition of a placebo (n = 157) vs staying on an AI in the form of anastrozole or letrozole and CDK4/6 inhibitor with a placebo (n = 158). The primary end point of the study was progression-free survival (PFS).
Earlier data showed that camizestrant plus continued CDK4/6 inhibition significantly improved PFS vs continued treatment with an AI and CDK4/6 inhibitor in this population.2 The median PFS in the camizestrant arm was 16.0 months (95% CI, 12.7-18.2) vs 9.2 months (95% CI, 7.2-9.5) in the AI arm (adjusted HR, 0.44; 95% CI, 0.31-0.60; P < .0001). It was also reported that camizestrant reduced the risk of clinically meaningful deterioration in global health status/quality of life (GHS/QOL) per the EORTC QLQ-C30 questionnaire. The median TTD with camizestrant was 21.0 months (95% CI, 13.8-NC) vs 6.4 months (95% CI, 2.8-14.0) with AI (adjusted HR, 0.54; 95% CI, 0.34-0.84).
In a past exclusive interview with OncLive®, Hope S. Rugo, MD, a professor in the Department of Medical Oncology & Therapeutics Research, division chief of Breast Medical Oncology, and director of the Women’s Cancers Program at City of Hope, discussed earlier QOL data from SERENA-6 following its presentation at the 2025 ASCO Annual Meeting.3 “Camizestrant isn’t an [FDA]-approved drug yet and this approach isn’t approved yet. We’re waiting to hear from the regulatory reviewers, but I assume this approach to treatment will be approved in less than a year.”
At the 2025 ESMO Congress, Mayer shared additional PRO data.1
Questionnaires were administered every 4 weeks for the first 12 weeks. “Please note this is earlier and more frequent than clinical tumor assessments,” Mayer said. They were then administered every 8 weeks until second progression or death to capture long-term effects on QOL. She added that PRO analyses were predefined and included secondary end points for TTD in pain and physical functioning, as well as arm and breast symptoms. “A trial-specific meaningful change threshold in deterioration was estimated using blinded study data from key domains,” she said.
Compliance rates for the questionnaires were comparable between treatment arms.
Additional information shared from the EORTC QLQ-C30 questionnaire showed that with regard to cognitive functioning, the median TTD with camizestrant was 23.0 months vs NR with AI (HR, 0.92; 95% CI, 0.57-1.50). In terms of social functioning, the median TTD in the respective arms was 34.1 months vs 15.9 months (HR, 0.80; 95% CI, 0.50-1.28). Per the EORTC QLQ-BR23 questionnaire, the median TTD with regard to breast symptoms with camizestrant was NR vs NR with AI (HR, 0.59; 95% CI, 0.28-1.24). With regard to arm symptoms, the median TTD in the respective arms was also NR and NR (HR, 0.69; 95% CI, 0.34-1.39).
Mayer noted that the findings support the delay in TTD and reduced risk of deterioration in GHS/QOL that had been previously reported.
“These PRO results from SERENA-6 support camizestrant and CDK4/6 inhibitor as a potential new treatment strategy to benefit patients with hormone receptor–positive/HER2-negative advanced disease and emergence of ESR1 mutation ahead of disease progression during first-line therapy,” Mayer concluded.
In a prior exclusive interview with OncLive,4 Mayer discussed ESR1 mutation detection by ctDNA liquid biopsy in SERENA-6. “Patients prefer [mutation testing with ctDNA] as it is noninvasive…and we [saw] in the SERENA-6 study that it is feasible to do…in a serial manner.”
In the full interview, Mayer expanded on how the SERENA-6 trial set out to address the development of endocrine resistance driven by ESR1 mutations in hormone receptor–positive, HER2-negative metastatic breast cancer; spotlighted primary data from the study; and explained how these findings could enable earlier detection of endocrine resistance and earlier treatment modifications to optimize patient outcomes in this disease setting.5
Disclosures: Mayer disclosed receipt of personal fees as a consultant for AstraZeneca, Eli Lilly, Genentech, Aktis Oncology, and Novartis.
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