Roche announced that its experimental oral selective estrogen receptor degrader (SERD), giredestrant, significantly reduced the risk of invasive disease recurrence or death by 30% compared with standard-of-care endocrine therapy (SoC-ET) in patients with ER-positive, HER2-negative early-stage breast cancer, according to interim results from the Phase III lidERA Breast Cancer Study.

The study enrolled 4,100 patients, with medium- or high-risk stage I-III disease, with participants randomised to receive adjuvant giredestrant or standard-of-care endocrine therapy. At three years of follow-up, 92.4% of patients receiving giredestrant were alive and free of invasive disease, versus 89.6% in the SoC-ET arm. Giredestrant also achieved a 31% reduction in the risk of distant recurrence (hazard ratio 0.69 for distant recurrence-free interval).

According to Roche, this is the first time an oral SERD has demonstrated superior invasive disease-free survival (iDFS) in the adjuvant setting, marking what many consider the first major advance in hormone-receptor-positive early breast cancer treatment in more than 20 years. CMO Levi Garraway described the results as “transformational”.

While overall survival (OS) data remain immature, safety was described as manageable and consistent with known profiles; no new adverse-event patterns emerged at this interim analysis.

Why it matters

  • ER-positive breast cancer accounts for ~70% of all breast cancer cases; standard adjuvant endocrine therapy often fails to prevent recurrence in a substantial fraction of patients.
  • First-generation oral SERD Oserdu (elacestrant), from Menarini, was approved in the US in January 2023 for ER+, HER2- breast cancer but focused on tumors with ESR1 mutations in the second-line setting.
  • Giredestrant is under stdy in both early and advanced settings and could potentially reshape care for early-stage ER+ disease.

The full data was presented this week at the San Antonio Breast Cancer Symposium (SABCS). Roche says it will be seeking regulatory approvals based on these results — a successful filing could make giredestrant the first next-generation oral SERD used in the curative adjuvant breast cancer setting.