A Turning Point for Giredestrant
Roche has announced a phase 3 success for its investigational oral selective estrogen receptor degrader (SERD) giredestrant, marking a turnaround from earlier trial setbacks. The company reported that the therapy met co-primary endpoints in the evERA trial, a study evaluating its use in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer.
Overcoming Past Challenges
Giredestrant has faced challenges in the past, including a failed midphase trial in 2022 that contributed to declining confidence in oral SERDs. That year also saw Sanofi’s amcenestrant fail a pivotal study. Since then, other candidates in the same class have gained ground, including Menarini’s Orserdu and AstraZeneca’s camizestrant.
evERA Trial Details and Results
The evERA trial enrolled patients whose disease had progressed following treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy. Participants received either giredestrant in combination with everolimus or a standard-of-care endocrine therapy plus everolimus.
Roche reported that the giredestrant combination demonstrated statistically significant and clinically meaningful improvements in progression-free survival in both the intention-to-treat and ESR1-mutated populations. Overall survival data were immature at the time of analysis, though a positive trend was observed. Follow-up for further analysis is ongoing.
According to Roche, the study population was enriched for ESR1-mutated patients, though the company has not disclosed the proportion of such patients or detailed results for those with ESR1-wild-type disease. The company noted that outcomes beyond the ESR1-mutated group could influence broader treatment prospects for oral SERDs.
Safety and Clinical Significance
Roche stated that the giredestrant combination was well tolerated, with adverse events aligning with known safety profiles of the component therapies and no new safety signals observed. The company highlighted that this is the first positive head-to-head phase 3 trial investigating an all-oral SERD-containing regimen against a standard-of-care combination.
“These results show that the giredestrant combination provided a meaningful benefit for ER-positive breast cancer patients whose disease has progressed following treatment with a CDK inhibitor,” said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development. He added that the company intends to engage with regulatory authorities with the goal of making the regimen available to patients.
Addressing Unmet Needs in Breast Cancer
ER-positive breast cancer represents approximately 70% of breast cancer cases and remains difficult to manage due to biological complexity and resistance to endocrine therapies. Roche indicated that combination regimens such as giredestrant plus everolimus could help address disease progression risks, while the all-oral format may reduce treatment burden by avoiding injections.
Future Outlook and Regulatory Submission
The company emphasized that the evERA trial is one component of a larger clinical development program for giredestrant, which spans multiple treatment settings. Additional data expected in 2026 from the persevERA and lidERA trials are anticipated to provide further clarity on the candidate’s role across first-line and adjuvant settings.
Roche confirmed that data from the evERA study will be submitted to health authorities for review.
Looking forward, Roche is planning to submit the evERA data to regulatory authorities while simultaneously advancing its broader giredestrant program. Two additional trials—persevERA and lidERA—are expected to yield further insights in first-line and adjuvant settings. Roche’s long-term goal is to establish giredestrant as a backbone therapy across multiple disease stages, leveraging the oral format to ease treatment burden on patients. The company will also need to navigate reimbursement discussions, comparative positioning vs other emerging SERDs or PROTACs, and the timing of label expansion across geographies.
With this successful readout, Roche’s giredestrant may represent a turning point in breast cancer therapeutics, reviving hope for oral SERDs and reasserting Roche’s leadership in oncology innovation.
