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A lot was covered but summary of 7 main studies we touched on during Metastatic HR+ #BreastCancer #SABCS highlights w/ @hoperugo: ✅...
Metastatic HR+ #BreastCancer #SABCS highlights w/ @hoperugo: ✅ #AMBRE ✅ #MONALEESA ✅ #VIKTORIA1 ✅...
#ESMO25 Managing HR+/HER2– mBC in 2025 💬An update is likely following the evERA and VIKTORIA-1 trials From Dr. William Gradishar's presentation👇
#SABCS2025 Honored to present this exciting data. Efficacy seen regardless of mESR1 or mPIK3CA with ela+eve. Data immature for abema. EVERA also shows benefit with giredestrant/EVE...
@ElisaAgostinett @OncoAlert No benefit among those patients WITHOUT ESR1m. Although ITT was significant with high % of pts with ESR1m, ⚠️ benefit is NOT in all-comers!!! ⚠️
Ember 3 updated results. Imlu maintaining benefit. Combo benefit similar to evera trial although here benefit regardless of esr1m. Would love to see the combo approved to allow us more options for...
#ESMO25 EVeRa (Phase III): Giredestrant + everolimus doubled PFS vs SOC ET + everolimus post-CDK4/6 in HR+/HER2– MBC ESR1 mut population; 10 mo vs 5.4 mo in ESR1-mut tumors. No major...
#ESMO25 Breaking the 6-Month PFS Ceiling after CDK4/6 Inhibition
#ESMO25 @elmayermd presents the very nice data from EVERA combining giredestrant/everolimus vs SOC ET/everolimus with marked improvement in PFS and ORR in mESR1 and ITT. ORR...
Qualification with EVERA. Biomarker data at SABCS tomorrow! Note PFS in non ESR1m subgroup similar. ORR better.
The EVERA tag covers two complementary trials targeting the mTOR pathway in HR+/HER2- advanced breast cancer. BOLERO-2 is the landmark Phase III trial that established everolimus (Afinitor) plus exemestane as a treatment option for postmenopausal women with advanced HR+/HER2- breast cancer progressing on nonsteroidal aromatase inhibitors. The newer Phase III evERA Breast Cancer trial (Roche) evaluates giredestrant, an investigational oral selective estrogen receptor degrader, combined with everolimus versus standard-of-care endocrine therapy plus everolimus in patients who have progressed after CDK4/6 inhibitors and endocrine therapy.
BOLERO-2 was a Phase III, international, double-blind, 1:1 randomized, placebo-controlled trial of 724 postmenopausal women. Patients received everolimus 10 mg/day plus exemestane 25 mg/day or placebo plus exemestane. The evERA trial is a Phase III, randomized, open-label, multicentre study enriched for ESR1-mutated patients, comparing giredestrant plus everolimus to physician's choice endocrine therapy plus everolimus.
BOLERO-2 enrolled postmenopausal women with advanced HR+/HER2- breast cancer whose disease recurred or progressed during or after treatment with nonsteroidal aromatase inhibitors (letrozole or anastrozole). The evERA trial enrolled patients with ER+/HER2- locally advanced or metastatic breast cancer previously treated with a CDK4/6 inhibitor and endocrine therapy.
BOLERO-2: Everolimus 10 mg daily plus exemestane 25 mg daily versus placebo plus exemestane. evERA: Giredestrant plus everolimus versus standard-of-care endocrine therapy plus everolimus.
BOLERO-2 primary endpoint: investigator-assessed PFS. Key secondary endpoint: OS. evERA co-primary endpoints: investigator-assessed PFS in the ITT population and in the ESR1-mutated population. Secondary endpoints: OS, ORR, DoR, CBR, and safety.
In BOLERO-2, everolimus plus exemestane more than doubled median PFS versus placebo plus exemestane. By local investigator assessment, median PFS was 7.8 months vs. 3.2 months (HR 0.45; 95% CI: 0.38-0.54; p<0.0001). By independent central review, median PFS was 11.0 months vs. 4.1 months (HR 0.38; 95% CI: 0.31-0.48; p<0.0001). In the evERA trial, giredestrant plus everolimus demonstrated median PFS of 8.77 months vs. 5.49 months in the ITT population (HR 0.56; 95% CI: 0.44-0.71; p<0.0001). In ESR1-mutated patients, median PFS was 9.99 vs. 5.45 months (HR 0.38; 95% CI: 0.27-0.54; p<0.0001).
In BOLERO-2, adding everolimus to exemestane did not confer a statistically significant improvement in OS. Median OS was 31.0 months (95% CI: 28.0-34.6) vs. 26.6 months (95% CI: 22.6-33.1) with placebo plus exemestane (HR 0.89; 95% CI: 0.73-1.10; p=0.14). In the evERA trial, OS data were immature at the time of analysis but showed a clear positive trend: ITT OS HR 0.69 (95% CI: 0.47-1.00; p=0.0473); ESR1-mutated OS HR 0.62 (95% CI: 0.38-1.02; p=0.0566).
In BOLERO-2, the most common adverse reactions (incidence 30% or greater) were stomatitis, infections, rash, fatigue, diarrhea, and decreased appetite. The most common grade 3-4 adverse reactions (incidence 2% or greater) were stomatitis, infections, hyperglycemia, fatigue, dyspnea, pneumonitis, and diarrhea. Serious risks include pneumonitis, severe infections, and kidney failure. In the evERA trial, the giredestrant combination was well tolerated with no new safety signals and notably no photopsia.
BOLERO-2 established everolimus as the first mTOR inhibitor approved for advanced HR+/HER2- breast cancer, targeting the PI3K/AKT/mTOR resistance pathway. However, the lack of OS benefit and significant toxicity profile (particularly stomatitis) have limited its clinical uptake, especially as CDK4/6 inhibitors became the preferred first-line approach. The evERA trial represents a potential resurgence of everolimus-based therapy, demonstrating that giredestrant plus everolimus could become the first oral SERD combination in the post-CDK4/6 inhibitor setting, with particular benefit in ESR1-mutated patients.
