In patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, the progression-free survival (PFS) benefit seen with the oral selective ER degrader giredestrant plus everolimus over standard endocrine therapy (ET) plus everolimus did not come at the expense of a worse quality of life, new data showed.

Patients treated with giredestrant plus everolimus were more apt to say they were “not at all” bothered by treatment side effects during therapy, said study author Miguel Martin, MD, PhD, during his presentation of the new safety and patient-reported outcome (PRO) data from the phase 3 evERA BC trial.

At cycle 2 day 1, 45% of patients in the giredestrant group reported no bother from adverse events compared with 32% in the ET group. Similar trends favoring giredestrant were seen across later treatment cycles, reported Martin of Complutense University, Madrid, Spain, at ESMO Breast Cancer 2026.

PRO data suggested that the overall treatment burden was comparable between the two regimens. Similar proportions of patients reported worsening of symptoms such as nausea, vomiting, diarrhea, fatigue, hot flashes, and joint pain during treatment. Symptom severity before treatment was balanced across the two groups, and most on-treatment symptom-worsening rates were comparable.

The safety profiles were similar between patients in the treatment and control groups as well, with adverse events of stomatitis and pneumonitis reported as mostly low grade.

The evERA BC trial enrolled 373 patients with ER-positive, HER2-negative advanced breast cancer who had received one to three prior lines of therapy and had progressed during or after treatment with a cyclin-dependent kinase 4 and 6 inhibitor plus ET.

Patients were randomly assigned (1:1) to receive either oral giredestrant 30 mg daily plus everolimus 10 mg or standard ET (exemestane, fulvestrant, or tamoxifen) plus everolimus. Approximately 55% of patients had ESR1-mutated tumors at baseline, a subgroup known to develop resistance to endocrine therapies.

The primary results showed that giredestrant plus everolimus demonstrated a statistically significant improvement in PFS in both the overall study population (hazard ratio [HR], 0.56) and in patients with ESR1-mutated tumors (HR, 0.38).

The median time to deterioration in physical functioning numerically favored the giredestrant group (10.4 vs 7.8 months). Pain deterioration was also numerically delayed with giredestrant (7.5 vs 5.7 months). Overall health-related quality of life was maintained for similar durations between treatment groups.

Any-grade pneumonitis occurred in 24.2% of patients receiving giredestrant plus everolimus and 17.2% of patients receiving ET plus everolimus. Most cases were grade 1 or 2 and reversible. Rates of grade 3 or 4 pneumonitis were low and comparable between groups, with no grade 5 events reported. More than three quarters of pneumonitis events resolved in both groups.

A major focus of Martin’s presentation was stomatitis, a common toxicity associated with everolimus. In the evERA BC trial, dexamethasone mouthwash prophylaxis — which was strongly recommended and used in about two thirds of patients overall — appeared to reduce the severity of stomatitis and shift events toward lower-grade disease, he noted.

Among patients receiving giredestrant plus everolimus, grade 2 stomatitis occurred in 14.4% of patients receiving prophylaxis compared with 21.1% of those without prophylaxis. Grade 3 stomatitis was numerically lower with dexamethasone mouthwash, occurring in 1.8% vs 4.2%, respectively. Similar patterns were observed in the ET plus everolimus group.

Martin said the prophylaxis delayed the median time to stomatitis onset from 13 days to 20 days in the giredestrant group and from 14.5 to 25 days in the ET group. Treatment modifications or discontinuation due to stomatitis remained low in both groups, and stomatitis recovery rates were high overall, with or without prophylaxis.

Study discussant Ines Vaz-Luis, MD, PhD, noted that the giredestrant plus everolimus combination delivered a “meaningful” PFS benefit, and the safety and PRO data are “reassuring” and aligned with clinician-reported toxicities.

She highlighted stomatitis as an “actionable safety story,” emphasizing that dexamethasone mouthwash prophylaxis reduced grade 2 stomatitis and delayed symptom onset, although not all patients received preventive treatment.

“The take-home is that supportive care should be part of the regimen and not optional add-on,” Vaz-Luis, who is a medical oncologist at Gustave Roussy and the University of Paris-Saclay in Paris, France, told meeting attendees.

The study was funded by F. Hoffmann-La Roche Ltd. Vaz-Luis disclosed having relationships with Amgen, AstraZeneca, Pfizer/Edimark, Novartis, Sandoz, Chugai Pharmaceutical, Servier Monde, Servier International Research Institute, and Doctaforum Medical Marketing SL.