Giredestrant Improves PFS in ER+, HER2– Breast Cancer
The evERA study reveals promising results for giredestrant in treating advanced ER-positive breast cancer, enhancing progression-free survival for patients.
The phase 3 evERA study (NCT05306340) investigating the novel agent giredestrant plus everolimus for the treatment of estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer met both co-primary end points, demonstrating statistically significant and clinically meaningful improvements in progression-free survival (PFS) in the intent-to-treat and ESR1-mutant populations.1
evERA is the first positive head-to-head phase 3 study evaluating an all-oral selective estrogen receptor degrader (SERD)-containing regimen vs a standard-of-care combination.
Overall survival (OS) data were immature at the time of this analysis but demonstrated a positive trend. Full data will be presented at an upcoming medical meeting and shared with regulatory authorities.
“These results show that the giredestrant combination provides a meaningful benefit for ER-positive breast cancer patients whose disease has progressed following treatment with a CDK inhibitor,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, in a press release. “We look forward to discussing these results with regulatory authorities with the goal of making this giredestrant-based regimen available to many people with advanced ER-positive breast cancer.”
Regarding safety, the giredestrant combination was well tolerated, and the observed adverse events were consistent with the known safety profiles of the individual agents.
As ER-positive breast cancer accounts for about 70% of cases, the need for effective treatments is imperative, especially for patients with disease resistant to endocrine therapies and in the post CDK inhibitor setting. These positive findings offer a new avenue for patients who face increased risks of disease progression and poor outcomes.
What is the Phase 3 evERA Study of Giredestrant Investigating?
evERA has enrolled 373 patients and randomized them to receive giredestrant or physician’s choice of exemestane, fulvestrant, or tamoxifen plus everolimus.2 Along with the primary end point of PFS, secondary end points include OS, objective response rate, duration of response, clinical benefit rate, health-related quality of life, incidence of vital sign abnormalities, incidence of laboratory abnormalities, and plasma concentration of giredestrant at specified time points.
Patients were required to have locally advanced unresectable or metastatic breast adenocarcinoma not amenable to treatment with curative intent and have received prior endocrine therapy in combination with a CDK4/6 inhibitor in the metastatic or adjuvant settings. They were also required to have documented ER-positive/HER2-negative tumors, an ECOG performance status of 0 to 1, and have measurable disease per RECIST v1.1 or evaluable bone metastases. Those who previously received treatment with another oral SERD, who experienced progression on more than 2 prior lines of systemic endocrine therapy, who received prior chemotherapy for locally advanced unresectable or metastatic disease, with active cardiac disease or history of cardiac dysfunction, with a known active uncontrolled or symptomatic central nervous system metastases, or who are pregnant or breastfeeding were not eligible for study enrollment.
The study recruited patients across 171 global sites and has a planned completion date of October 15, 2026.
References:
- Positive Phase III Results Show Genentech’s Giredestrant Significantly Improved Progression-Free Survival in ER-positive Advanced Breast Cancer. News release. Genentech. September 22, 2025. Accessed September 23, 2025. https://tinyurl.com/43mhbd4y
- A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician’s Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer). ClinicalTrials.gov. Updated August 13, 2025. Accessed September 23, 2025. https://clinicaltrials.gov/study/NCT05306340