FDA Accepts Roche’s NDA For Giredestrant Plus Everolimus In ESR1-Mutated ER-Positive Advanced Breast Cancer

Roche announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for giredestrant, an investigational oral therapy, in combination with everolimus. The regimen is intended for adults with oestrogen receptor (ER)-positive, HER2-negative, ESR1-mutated locally advanced or metastatic breast cancer whose disease has progressed following prior endocrine-based therapy. The FDA has set a target action date of 18 December 2026. If approved, the combination could become the first oral selective oestrogen receptor degrader (SERD)-based regimen available in the post-CDK4/6 inhibitor setting.

The NDA submission is supported by results from the phase III evERA Breast Cancer study, which demonstrated significant clinical benefit. Giredestrant plus everolimus reduced the risk of disease progression or death by 44% in the intention-to-treat (ITT) population and by 62% in patients with ESR1 mutations compared to standard endocrine therapy plus everolimus. In ESR1-mutated patients, median progression-free survival (PFS) reached 9.99 months versus 5.45 months in the comparator arm (HR=0.38; p<0.0001). In the ITT population, median PFS was 8.77 months compared with 5.49 months (HR=0.56; p<0.0001).

“The clinically meaningful benefit seen with giredestrant could enable an important new treatment option to help delay disease progression or death in people with advanced, ER-positive breast cancer,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “This acceptance marks a first step towards establishing the giredestrant combination as a new standard of care in this population.”

Overall survival (OS) data remain immature, though interim analyses indicate a favourable trend in both the ITT and ESR1-mutated groups. The safety profile of the combination was manageable and aligned with the known characteristics of each individual therapy, with no unexpected adverse events reported, including no cases of photopsia. Roche plans to continue OS follow-up and use evERA data to support regulatory submissions in additional global markets.

ER-positive breast cancer represents roughly 70% of all breast cancer diagnoses, and resistance to endocrine therapy, particularly after CDK4/6 inhibitors- remains a significant clinical challenge. Roche’s broader giredestrant development programme spans early-stage and advanced disease settings. Following the positive phase III evERA results, additional studies such as lidERA in early-stage disease and persevERA in first-line ER-positive breast cancer aim to further establish giredestrant’s role across treatment lines. Roche intends to submit lidERA data to global health authorities in the coming weeks, reinforcing its strategy to expand treatment options for patients with ER-positive breast cancer