Roche has lifted the lid on the data behind its second phase 3 giredestrant win, linking the oral selective estrogen receptor degrader (SERD) to a 30% reduction in the risk of invasive disease recurrence or death.
The Swiss drugmaker reported that its phase 3 lidERA trial met its primary endpoint in November. LidERA enrolled 4,100 patients with ER-positive, HER2-negative early-stage breast cancer to receive Roche’s oral SERD candidate or standard-of-care endocrine therapy. Roche used the 2025 San Antonio Breast Cancer Symposium to share the numbers behind its top-line victory.
The analysis of LidERA’s primary endpoint showed that 6.7% of patients on giredestrant had developed invasive cancer or died, compared to 9.4% of people in the control arm.
Roche calculated a hazard ratio of 0.7—correlating to a 30% risk reduction—and a statistically significant p-value. The drugmaker said the oral SERD’s efficacy advantage was consistent across clinically relevant subgroups. At a press event, UCLA Health’s Aditya Bardia, M.D., said giredestrant was superior to aromatase inhibitors with a hazard ratio of 0.73 and to tamoxifen with a hazard ratio of 0.53.
CDK 4/6 inhibitors weren’t approved for adjuvant use when the trial was designed, Bardia said. The FDA subsequently authorized Eli Lilly’s Verzenio and Novartis’ Kisqali in the setting. Some participants in lidERA wouldn’t have been eligible to take Verzenio and Kisqali, Bardia said, but there is overlap in the eligible populations. The drugs could compete for—and be combined in—the same patient populations.
“It is a discussion related to the side effects and efficacy that will guide the use. At this time, we don't have data of giredestrant in combination with [Verzenios], but that study is ongoing,” Bardia said. “Maybe for patients with high-risk disease, some physicians would want the best endocrine option along with a CDK 4/6 inhibitor.”
After three years, 92.4% of patients in the giredestrant arm were alive and free of invasive disease versus 89.6% in the control arm. The gap between the two arms after three years—2.8 percentage points—was slightly wider than after two years. Roche also linked giredestrant to a 31% risk reduction on an endpoint that looked at time until the first appearance of invasive breast cancer recurrence at a distant site.
As Roche said in its top-line release, the study’s secondary overall survival (OS) endpoint is yet to reach statistical significance but is trending in the right direction. At the interim analysis, 2.7% of people on giredestrant had died, compared to 3.4% of the patients on standard of care. OS follow-up will continue to the next analysis.
Roche said giredestrant was well tolerated, adding that adverse events were manageable and consistent with the molecule's known safety profile. Bradycardia, the medical term for a slow heart rate, was seen in 11.3% of people on giredestrant, compared to 3.2% of patients on standard of care. However, most of the cases were asymptomatic, and no patients had grade 3 or 4 bradycardia.
Going into the adjuvant readout, analysts identified gastrointestinal toxicity as an area giredestrant may have a disadvantage over its competition. Diarrhea and constipation were more common on giredestrant than standard of care. All cases of constipation and most cases of diarrhea were grade 1 or 2.
Roche has identified tolerability as a factor that could encourage physicians to prescribe giredestrant over existing adjuvant breast cancer drugs. While joint pain was the most common treatment-emergent adverse event in both cohorts, the proportion of patients who stopped treatment because of the side effect and other musculoskeletal disorders was lower on giredestrant, 1.8%, than on the control, 4.4%.
The readout positions Roche to become the first company to try to establish an oral SERD in the adjuvant market. While AstraZeneca, Eli Lilly and Menarini are all studying oral SERDs in the setting, Roche said lidERA is the first study in the class to show a significant benefit in adjuvant use. The Swiss drugmaker is preparing to share the data with health authorities.
Editor's note: This article was updated at 9:45 a.m. ET on Dec. 10 to add comments from oncologist Aditya Bardia, M.D.