Camizestrant Plus CDK4/6 Inhibitors Shows PFS Benefit in HR+/HER2- Breast Cancer
Camizestrant combined with CDK4/6 inhibitors improved progression-free survival in HR+/HER2- advanced breast cancer with ESR1 mutations in the SERENA-6 trial.
Breast Cancer Therapy: © vitanovski - stock.adobe.com
In the phase 3 SERENA-6 trial (NCT04964934), the investigational selective estrogen receptor degrader (SERD) camizestrant, in combination with any of 3 CDK4/6 inhibitors—palbociclib (Ibrance), ribociclib (Kisqali), or abemaciclib (Verzenio)—led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs the standard-of-care treatment of an aromatase inhibitor plus a CDK4/6 inhibitor in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer with emergent ESR1 mutations.1
The primary end point of the study, PFS, demonstrated a favorable outcome for the camizestrant combination. Although key secondary end points, including time to second disease progression (PFS2) and overall survival (OS), remain immature, a trend toward improved PFS2 was observed.
Other secondary end points, including chemotherapy-free survival, objective response rate per RECIST 1.1 criteria, and clinical benefit rate at 24 weeks, also showed promising results. The ongoing study will continue to monitor these secondary end points.
"Patients have an urgent need for new treatments that delay disease progression on first-line endocrine-based therapies,” said François-Clément Bidard, MD, PhD, head of the Translational Research Group and a professor of medicine in the Department of Medical Oncology at Institut Curie & UVSQ/Université Paris-Saclay in France, in a press release. “The results from SERENA-6 show that switching from an aromatase inhibitor to camizestrant in combination with any of the 3 CDK4/6 inhibitors after emergence of an ESR1 mutation delays progression of disease and extends the benefit of first-line treatment, representing an important step forward for patients, and a potential shift in clinical practice."
The safety profile of camizestrant when given in combination with the CDK4/6 inhibitors was consistent with the known safety profiles of each of the individual agents. No new safety concerns were seen, and the rates of treatment discontinuation were low. Further, there were no significant differences between the investigational and control arms.
"These impressive results demonstrate the versatility of camizestrant in combination with all the widely approved CDK4/6 inhibitors to provide a well-tolerated new potential treatment option in the first-line setting for the 1 in 3 patients with HR-positive/HER2-negative advanced breast cancer whose tumors develop ESR1 mutations during treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor,” stated Susan Galbraith, PhD, executive vice president, Oncology Hematology R&D at AstraZeneca, in the press release. “This critical read-out moves us one step closer to realizing the potential of camizestrant to become a new standard-of-care as we look to shift the treatment paradigm and establish this new endocrine therapy backbone in HR-positive breast cancer.”
Trial Design and Study Population
SERENA-6 is a global, double-blind, randomized study that enrolled 315 patients with HR-positive/HER2-negative metastatic breast cancer with a detectable ESR1 mutation.2 Eligible patients were required to have an ECOG performance status of 0 or 1, sufficient organ and bone marrow function, and be undergoing initial treatment with letrozole or anastrozole combined with either palbociclib, abemaciclib, or ribociclib.
In the investigational arm of the study, patients were given oral camizestrant at a dose of 75 mg daily in combination with palbociclib, ribociclib, or abemaciclib. The CDK4/6 inhibitors were administered at their respective approved dose ranges.
In the control arm, patients received either anastrozole or letrozole combined with 1 of the same CDK4/6 inhibitors at equivalent doses.
Notably, the phase 3 SERENA-6 study is the first global, double-blind, registrational trial to use a circulating tumor DNA-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression.1
Additional findings from the SERENA-6 trial are expected to be presented at an upcoming medical meeting, as well as shared with global regulatory authorities.
REFERENCES
Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 phase III trial. News release. AstraZeneca. February 26, 2025. Accessed February 26, 2025. https://tinyurl.com/53apfkmu
Phase III study to assess AZD9833+ CDK4/6 inhibitor in HR+/HER2-MBC with detectable ESR1m before progression (SERENA-6) (SERENA-6). ClinicalTrials.gov. Updated January 10, 2025. Accessed February 26, 2025. https://clinicaltrials.gov/study/NCT04964934
