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Positive
- PFS risk reduction 44% in ITT (HR=0.56)
- PFS risk reduction 62% in ESR1-mutated (HR=0.38)
- Median PFS 8.77 vs 5.49 months (ITT)
- Median PFS 9.99 vs 5.45 months (ESR1-mutated)
Negative
- Overall survival data immature at analysis (follow-up ongoing)
- OS estimates are trends, not yet statistically confirmed
10/18/2025 – 01:00 AM
Roche (SIX: RO, ROG; OTCQX: RHHBY) has announced encouraging top-line results from its Phase III evERA trial evaluating giredestrant in combination with everolimus for patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with CDK4/6 inhibitors and endocrine therapy. The data, presented at the European Society for Medical Oncology (ESMO) Congress 2025, demonstrate a statistically significant and clinically meaningful improvement in progression-free survival (PFS).
- Giredestrant plus everolimus reduced the risk of disease progression or death by 44% in the intention-to-treat (ITT) population.
- The risk reduction was even more pronounced (62%) in patients with ESR1 mutations.
- The combination therapy was generally well-tolerated, with no unexpected safety signals.
- While overall survival (OS) data is still maturing, a positive trend has been observed in both the ITT and ESR1-mutated populations, suggesting a potential long-term benefit.
The evERA trial results mark a significant step forward in addressing the unmet need for effective treatments post-CDK4/6 inhibitor failure. CDK4/6 inhibitors, while effective, often lead to acquired resistance, necessitating new therapeutic strategies. Giredestrant, a next-generation selective estrogen receptor degrader (SERD), offers a novel approach targeting the ER pathway. Combined with everolimus, an mTOR inhibitor, the combination targets crucial signaling pathways involved in breast cancer progression.
PFS Improvement: A Closer Look.
In the ITT population, the median PFS was 8.77 months in the giredestrant arm compared to 5.49 months in the control arm (HR=0.56; 95% CI: 0.44-0.71, p-value < 0.0001). For patients harboring ESR1 mutations, the median PFS jumped to 9.99 months with giredestrant versus 5.45 months in the comparator arm (HR=0.38; 95% CI: 0.27-0.54, p-value < 0.0001). This substantial improvement suggests a potential ability to overcome endocrine resistance, particularly in the ESR1-mutated subgroup, which is known to drive resistance to aromatase inhibitors.
Implications for Treatment Paradigm.
“These results are particularly exciting because they point to a potential new treatment option in a setting where options are limited,” commented a lead investigator on the trial. “The robust PFS benefit, combined with a manageable safety profile, could establish giredestrant plus everolimus as a new standard of care for patients who have progressed on CDK4/6 inhibitors.”
Analyst Perspective.
Analysts at Jefferies noted in a flash report that the data were “best case” and “strongly de-risks” the gidredestrant program. The investment bank highlighted that gidredestrant’s market potential is now meaningfully higher. The company’s potential to be the first all-oral option would be a major advantage to many patients.
The ongoing analysis of overall survival (OS) data is also of key importance. A positive trend in OS, even if not statistically significant at this interim analysis, suggests that the PFS benefit could translate into longer-term survival gains. Roche plans to submit the evERA data to health authorities globally, seeking regulatory approval to bring this potential new treatment option to patients as quickly as possible.
Looking Ahead: Technical and Commercial Considerations.
From a technical perspective, further research is warranted to understand the mechanisms of action of giredestrant and everolimus in overcoming endocrine resistance, particularly in the context of ESR1 mutations. Biomarker analysis from the evERA trial, including circulating tumor DNA (ctDNA) assessment, could provide valuable insights.
Commercially, the successful launch of giredestrant plus everolimus will depend on factors such as pricing, reimbursement, and physician adoption. Competition from other emerging therapies will also play a role. Nevertheless, given the significant unmet need and the compelling clinical data, giredestrant has the potential to become a significant revenue driver for Roche in the coming years.
The evERA trial represents a crucial advance for patients with ER-positive, HER2-negative advanced breast cancer. As the data matures and is submitted for regulatory review, the medical community awaits the potential arrival of a new treatment option that could improve outcomes for these individuals.
FAQ
What did Roche announce on 18 October 2025 about RHHBY and evERA phase III results?
Roche announced giredestrant plus everolimus significantly improved PFS versus standard‑of‑care, with 44% risk reduction in ITT and 62% in ESR1‑mutated patients.
How much did giredestrant plus everolimus improve median PFS in the RHHBY evERA trial?
Median PFS was 8.77 vs 5.49 months in ITT and 9.99 vs 5.45 months in ESR1‑mutated patients for giredestrant versus comparator.
Are overall survival results for RHHBY’s evERA study conclusive as of 18 October 2025?
No; OS data were reported as immature with a positive trend but require further follow‑up.
Was the giredestrant plus everolimus safety profile acceptable in the evERA trial (RHHBY)?
Yes; adverse events were manageable with no new safety signals observed, including no photopsia.
Which patient population showed the largest PFS benefit in the RHHBY evERA data?
The ESR1‑mutated population showed the largest PFS benefit, with a 62% reduced risk of progression or death (HR=0.38).
What is the clinical setting for Roche’s giredestrant plus everolimus results (RHHBY)?
The trial studied people with ER‑positive, HER2‑negative locally advanced or metastatic breast cancer previously treated with CDK4/6 inhibitors and endocrine therapy.
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