Dr O’Shaughnessy on Highly Anticipated Breast Cancer Data to Watch at ESMO 2025

“We’re going to get [data from] the evERA trial of giredestrant plus everolimus. We’ll have the survival data [from] monarchE which are important. However, the DESTINY-Breast11 and DESTINY-Breast05 [findings] will be real highlights of [ESMO 2025].”

Joyce A. O’Shaughnessy, MD, co-chair of Breast Cancer Research and chair of Breast Cancer Prevention Research at the Baylor Charles A. Sammons Cancer Center and The US Oncology Network, as well as a member of the Scientific Advisory Board for the US Oncology Research Network, discussed the breast cancer data she is most excited to see at the 2025 ESMO Congress.

The presentation of the phase 3 evERA trial (NCT05306340) data is highly anticipated, O’Shaughnessy began. This study investigated giredestrant (GDC-9545)—an oral selective estrogen receptor (ER) antagonist and degrader—in combination with everolimus (Afinitor) in patients with ER-positive, HER2-negative advanced breast cancer who have previously undergone treatment with a CDK4/6 inhibitor.

Furthermore, the meeting will feature the primary overall survival results from the phase 3 monarchE trial (NCT03155997). This study assessed adjuvant abemaciclib (Verzenio) administered in conjunction with endocrine therapy for the treatment of patients with high-risk, hormone receptor (HR)–positive, HER2-negative early breast cancer.

O'Shaughnessy also identified the phase 3 DESTINY-Breast11 (NCT05113251) and DESTINY-Breast05 (NCT04622319) trial data as true highlights of ESMO 2025. DESTINY-Breast11 is comparing different treatment sequences for patients with high-risk HER2-positive early breast cancer, including neoadjuvant fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) administered either alone or followed by a combination regimen of paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP), vs standard-of-care doxorubicin plus cyclophosphamide, followed by THP. DESTINY-Breast05 examined T-DXd vs ado-trastuzumab emtansine (Kadcyla) in patients with high-risk, HER2-positive primary breast cancer who have residual invasive disease after neoadjuvant therapy.

In addition to definitive efficacy and survival data, O'Shaughnessy expressed excitement about updated patient-reported outcome data from the phase 3 SERENA-6 trial (NCT04964934), which evaluated a switch from an aromatase inhibitor plus a CDK4/6 inhibitor to camizestrant plus a CDK4/6 inhibitor following the emergence of an ESR1 mutation during first-line therapy in patients with HR-positive, HER2-negative advanced breast cancer.

O’Shaughnessy also highlighted the potential significance of data from the phase 3 ASCENT-03 study (NCT05382299). This randomized trial compared sacituzumab govitecan-hziy (Trodelvy) with chemotherapy in patients with previously untreated, advanced triple-negative breast cancer (TNBC) who were ineligible for treatment with PD-(L)1 inhibitors.

Finally, O’Shaughnessy expressed excitement for the primary results from the randomized phase 3 TROPION-Breast02 trial (NCT05374512). This trial investigated the efficacy of datopotamab deruxtecan-dlnk (Datroway) vs chemotherapy in patients with locally recurrent inoperable or metastatic TNBC who were ineligible for PD-(L)1 inhibitor therapy.