Roche reports phase III persevERA results showing giredestrant plus palbociclib missed the primary PFS endpoint versus letrozole plus palbociclib in ER-positive metastatic breast cancer
Written By: Katherashala Dharan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Roche has reported topline results from the phase III persevERA trial evaluating the investigational oral selective estrogen receptor degrader (SERD) giredestrant in combination with palbociclib for patients with estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer.
The study did not meet its primary endpoint, as the combination failed to demonstrate a statistically significant improvement in progression-free survival (PFS) compared with the standard regimen of letrozole plus palbociclib in the intent-to-treat population. However, Roche noted that a numerical improvement in PFS was observed with the giredestrant-based regimen.
Safety findings from the trial showed that adverse events were manageable and consistent with the known safety profiles of the individual agents.
“While persevERA didn’t meet its primary objective, we remain confident in the potential of giredestrant as a future endocrine therapy option in ER-positive breast cancer,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. He added that the company sees a potential path forward for combining giredestrant with CDK4/6 inhibitors in adjuvant treatment settings, with further studies ongoing.
The persevERA trial (NCT04546009) enrolled 992 patients globally and compared giredestrant plus palbociclib with letrozole plus palbociclib as first-line treatment. The primary endpoint was investigator-assessed progression-free survival, while key secondary endpoints included overall survival, objective response rate, duration of response, and safety.
Roche stated that full results from the study will be presented at an upcoming medical meeting.
Despite the negative primary endpoint, the company continues to advance the giredestrant clinical programme. Another phase III study, pionERA, evaluating giredestrant with a physician’s choice of CDK4/6 inhibitor in endocrine-resistant ER-positive breast cancer, is expected to report results in 2027.
The update follows recent regulatory progress for the therapy. The U.S. Food and Drug Administration recently accepted Roche’s New Drug Application for giredestrant based on the phase III evERA study, while additional regulatory submissions using lidERA trial data are planned. More details on those developments are available in Pharmacally’s earlier coverage of the FDA NDA acceptance and the positive evERA trial results.
Reference
[Ad hoc announcement pursuant to Art. 53 LR] Roche provides update on phase III persevERA study in ER-positive advanced breast cancer, 09 March 2026, [Ad hoc announcement pursuant to Art. 53 LR] Roche provides update on phase III persevERA study in ER-positive advanced breast cancer
A Study Evaluating the Efficacy and Safety of Giredestrant Combined with Palbociclib Compared with Letrozole Combined with Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer), ClinicalTrials.gov ID NCT04546009, https://clinicaltrials.gov/study/NCT04546009
About the Writer
Katherashala Dharan Kumar, PharmD A dedicated Clinical Researcher with expertise in medical and scientific writing clinical trials, drug safety, and healthcare innovation. Actively contributes to research publications and clinical documentation focused on improving patient outcomes through evidence-based practices and ethical research standards. Believe that every complex data point has a human story waiting to be told. Focusing on providing actionable insights for clinical research.