Novel endocrine therapy giredestrant improves disease-free survival over standard of care for patients with early-stage breast cancer in phase III lidERA trial

(Press-News.org) SAN ANTONIO – The investigational, oral selective estrogen receptor degrader (SERD) giredestrant  given as an adjuvant therapy showed significant improvement in invasive disease-free survival (iDFS) compared with the current standard-of-care endocrine therapy in patients with early-stage, hormone receptor (HR)-positive, HER2-negative breast cancer, according to the results of the phase III IidERA trial presented at the San Antonio Breast Cancer Symposium (SABCS), held December 9-12, 2025.

“For patients with HR-positive breast cancer—which accounts for about 70% of breast cancer cases—effective adjuvant therapy at the early stage offers a real opportunity to eradicate micrometastatic disease and improve survival in the curative setting,” said presenter Aditya Bardia, MD, MPH, professor of medicine and director of translational research integration at the University of California, Los Angeles Jonsson Comprehensive Cancer Center. “Currently, up to a third of these patients eventually experience recurrence on or after adjuvant endocrine therapy for early breast cancer, and many struggle with tolerating treatment. A more effective, more tolerable treatment option is needed.”

In the global, randomized, open-label, multicenter trial, Bardia and colleagues enrolled patients with HR-positive, HER2-negative breast cancer in stages 1-3 to evaluate the safety and efficacy of giredestrant compared with the current standard-of-care therapies. All patients enrolled had received surgery and, if indicated, completed adjuvant or neoadjuvant chemotherapy. The median age of participants was 54, and 59% were postmenopausal.

In the randomized clinical trial, the researchers assigned 4,170 patients 1:1 to receive either 30 mg of giredestrant or one of four standard-of-care endocrine therapies selected at the discretion of the prescribing physician: tamoxifen, letrozole, anastrozole, or exemestane. Patients received their treatment daily for every 28-day cycle until five years had passed or unacceptable toxicity had occurred.

The researchers assessed patients for the primary endpoint of iDFS, and secondary endpoints included overall survival (OS) and distant recurrence-free interval (DRFI).

The trial met its primary endpoint at a prespecified interim analysis. After a median follow-up of 32.3 months, patients who received giredestrant had significantly better iDFS than their counterparts who received standard-of-care endocrine therapy and were 30% less likely to develop invasive disease progression at the time of follow-up.

The secondary endpoint of DRFI was also met. Patients who received giredestrant were 31% less likely than those in the standard-of-care arm to experience distant recurrence at the time of follow-up.

“Giredestrant demonstrated clinically meaningful superiority to currently well-established standard-of-care endocrine agents: aromatase inhibitors and tamoxifen,” Bardia said. “What is particularly striking and relevant is early separation of curves,” he added, referring to the preliminary OS data. Due to the limited follow-up window, the OS data were immature but showed a positive trend in favor of giredestrant over the standard of care, he explained.

The most common treatment-emergent adverse events (TEAEs) in both the giredestrant and standard-of-care arms were arthralgia, hot flashes, and headache (all of which were primarily low grade and nonnonserious), and the frequency of all of these TEAEs were similar between arms. Grade 3 and 4 TEAEs included hypertension and arthralgia. Few patients died of TEAEs (six and 16 patients died in the giredestrant and standard-of-care arms, respectively), with no treatment-related deaths in the giredestrant arm (one in the standard-of care arm).

Bradycardia—a known class effect of oral SERDs, according to Bardia—was higher in the giredestrant arm at 11.3% than in the standard-of-care arm at 3.2%. The majority were grade 1, asymptomatic, and nonserious, not requiring treatment interruption/discontinuation. Grade 2 adverse events (<1%) were confounded by concurrent conditions/antihypertensives, and all resolved. Treatment discontinuations due to TEAEs were numerically lower in the giredestrant arm at 5.3% than in the standard-of-care endocrine therapy arm at 8.2%. 

“For more than a quarter of a century, tamoxifen and aromatase inhibitors have remained the standard endocrine therapy option for patients with early breast cancer,” said Bardia. “Results from lidERA demonstrate clinical superiority of giredestrant to tamoxifen and aromatase inhibitors, placing giredestrant as a new standard in endocrine therapy for patients with early-stage, HR-positive, HER2-negative breast cancer.”

The study’s limitations include limited follow-up and immature OS data.

The study was funded by F. Hoffmann-La Roche Ltd. Bardia has served as a consultant and/or advisory board member to Pfizer, Novartis, Genentech, Merck, Menarini, Gilead Sciences, Alyssum Therapeutics, Vyome, Sanofi, Daiichi Sankyo/AstraZeneca, Bristol Myers Squibb, and Eli Lilly. Bardia has conducted contracted research for or received research grants from Genentech, Novartis, Pfizer, Merck, Sanofi, OnKure Therapeutics, Menarini, Gilead Sciences, Daiichi Sankyo/AstraZeneca, and Eli Lilly.

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