Camizestrant Plus Palbociclib Misses PFS End Point in SERENA-4 Trial

The phase 3 SERENA-4 trial (NCT04711252) of camizestrant (Etcamah) plus palbociclib (Ibrance) did not meet its primary end point of a statistically significant improvement in progression-free survival (PFS) vs anastrozole plus palbociclib in the upfront, 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.¹ A numerical improvement in PFS favoring the camizestrant combination was observed, although AstraZeneca, the sponsor, did not disclose hazard ratio, confidence interval, or P-value data.

Study Design

SERENA-4 is a global, double-blind trial that enrolled 1371 adult patients with newly diagnosed stage IV de novo or recurrent ER-positive, HER2-negative advanced breast cancer. Patients whose disease recurred after early-stage treatment had completed at least 24 months of standard adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen, with a minimum of 12 months elapsed since the final dose of adjuvant aromatase inhibitor therapy without progression on treatment. Participants were randomized to receive camizestrant, an oral selective estrogen receptor degrader (SERD) and complete ER antagonist, plus palbociclib, or anastrozole plus palbociclib. PFS by investigator assessment was the primary end point; secondary end points include overall survival (OS), PFS2, and health-related quality of life (HRQOL).

Safety and Next Steps

The safety profile of camizestrant plus palbociclib in SERENA-4 was consistent with the known safety profile of each agent, and no new safety signals were identified. Detailed efficacy and safety data from the trial will be shared at a later date.

Clinical Context and Limitations

The SERENA-4 result comes about a week after the FDA granted camizestrant accelerated approval for a narrower population: patients with ER-positive, HER2-negative advanced breast cancer who develop a detected or emergent ESR1 mutation during first-line endocrine-based therapy, based on the phase 3 SERENA-6 trial (NCT04964934).² SERENA-4, by contrast, tested camizestrant from the start of first-line treatment in an unselected ER-positive, HER2-negative population, without requiring evidence of an ESR1 mutation or any prior therapy for advanced disease.

Broader Development Program

Camizestrant is also being evaluated in the CAMBRIA-1 (NCT05774951) and CAMBRIA-2 (NCT05952557) trials, which together are expected to enroll approximately 10,000 patients with ER-positive, HER2-negative breast cancer at intermediate or high risk of recurrence in the early-disease setting.1 The trials are assessing camizestrant as monotherapy, in combination with a CDK4/6 inhibitor, and following CDK4/6 inhibitor treatment, and are part of what AstraZeneca describes as its most comprehensive oral SERD development program in early breast cancer.¹

"Whilst we are disappointed by the SERENA-4 outcome, it sharpens our focus on maximising the number of patients who can benefit from Etcamah today based on SERENA-6 and reinforces the importance of ESR1 testing for patients on first-line therapy. 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,” said Susan Galbraith, executive vice president, Oncology Haematology Research and Development, AstraZeneca, in a news release.

REFERENCES

1. Update on SERENA-4 Phase III trial of Etcamah in combination with palbociclib in upfront 1st-line advanced ER-positive breast cancer. News release. AstraZeneca. September 11, 2026. Accessed September 14, 2026. https://tinyurl.com/2b8uhuct

2. FDA grants accelerated approval to a new breast cancer treatment. FDA. September 4, 2026. Accessed September 14, 2026. https://tinyurl.com/yp4hyrjw