Camizestrant plus palbociclib did not significantly improve progression-free survival vs anastrozole plus palbociclib in the first-line SERENA-4 trial.
Camizestrant (Etcamah) plus palbociclib (Ibrance) did not meet the primary end point of a statistically significant improvement in progression-free survival (PFS) vs anastrozole plus palbociclib in the first-line treatment of patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer who had not received prior systemic therapy for advanced disease in the phase 3 SERENA-4 trial (NCT04711252).¹
A numerical improvement in PFS was observed in favor of the camizestrant combination, although it did not reach statistical significance. The safety profile of camizestrant plus palbociclib was consistent with the known profiles of each agent, and no new safety signals were seen. Detailed data from the trial are planned to be shared at a later date.
“Whilst we are disappointed by the SERENA-4 outcome, it sharpens our focus on maximizing the number of patients who can benefit from [camizestrant] today based on SERENA-6 and reinforces the importance of ESR1 testing for patients on first-line therapy,” Susan Galbraith, executive vice president of oncology hematology research and development at AstraZeneca, stated in a news release. “Early breast cancer represents an important opportunity, and we remain confident in the long-term potential of [camizestrant] in the early setting as we advance our broader programme.
SERENA-4 was a global, randomized, double-blind trial evaluating camizestrant plus palbociclib vs anastrozole plus palbociclib in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer. The trial enrolled 1371 adult patients who were newly diagnosed with stage IV de novo or recurrent disease and had not received systemic therapy for metastatic disease. Patients with recurrence from early-stage disease were required to have received at least 24 months of standard adjuvant endocrine therapy (an aromatase inhibitor or tamoxifen) with at least 12 months elapsed since the last dose of adjuvant aromatase inhibitor therapy and no disease progression during treatment.
SERENA-4 at a Glance
- SERENA-4 did not meet its primary end point of a statistically significant PFS improvement with camizestrant plus palbociclib vs anastrozole plus palbociclib.
- A numerical PFS improvement favoring the camizestrant combination was observed but was not statistically significant.
- The safety profile of the combination was consistent with the known profiles of each agent, with no new safety signals identified.
Patients were randomly assigned to receive oral camizestrant at 75 mg once daily plus palbociclib at 125 mg once daily for the first 21 days of each 28-day cycle, as well as an anastrozole placebo; or anastrozole at 1 mg once daily plus palbociclib on the same schedule and camizestrant placebo.2 Men and premenopausal women and men also received a luteinizing hormone–releasing hormone agonist.
Investigator-assessed PFS served as the primary end point, with secondary end points including overall survival, time to second disease progression, overall response rate, duration of response, time to chemotherapy, time to first subsequent therapy, clinical benefit rate, time to second subsequent therapy, and health-related quality of life.
The SERENA-4 result stands in contrast to that of SERENA-6, which enrolled patients with ER-positive, HER2-negative advanced breast cancer who had no evidence of progression on an aromatase inhibitor plus a CDK4/6 inhibitor given as initial endocrine-based therapy, had received no prior chemotherapy for advanced disease, and harbored an ESR1 mutation that was detected on ctDNA but absent on radiographic progression.3 Based on data from SERENA-6, camizestrant plus a CDK4/6 inhibitor (palbociclib, ribociclib [Kisqali], or abemaciclib [Verzenio])
Camizestrant is a next-generation oral selective ER degrader and complete ER antagonist that is administered once daily. The recommended dose in combination with a CDK4/6 inhibitor is 75 mg.
