Following the 2024 San Antonio Breast Cancer Symposium (SABCS), Paolo Tarantino, MD, and Matteo Lambertini, MD, PhD, co-hosted a live X Space with CancerNetwork® and spoke about updated trial findings that may impact the breast cancer treatment paradigm.

Tarantino is a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School. Lambertini is an associate professor and consultant in medical oncology at the University of Genova – IRCCS Policlinico San Martino Hospital in Genova, Italy.

Tarantino and Lambertini highlighted data from various studies that investigators presented at the Symposium, which included results on the use of treatment modalities such as antibody drug conjugates and CDK4/6 inhibitors. Some presentations of interest included the following:

· Phase 3 DESTINY-Breast06 Trial (NCT04494425)

o Patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow metastatic breast cancer were assigned to receive fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) or physician’s choice of therapy.

o Treatment with T-DXd improved progression-free survival (PFS) among patients with a time to progression on frontline endocrine therapy of less than 6 months (HR, 0.38; 95% CI, 0.25-0.59), 6 to 12 months (HR, 0.69; 95% CI, 0.43-1.12), and more than 12 months (HR, 0.67; 95% CI, 0.51-0.88).

o PFS improved with T-DXd regardless of disease burden.

· Phase 3 EMBER-3 Trial (NCT04975308)

o Investigators evaluated 3 treatment arms—imlunestrant (LY3484356) monotherapy, fulvestrant (Faslodex) or exemestane (Aromasin), and imlunestrant in combination with abemaciclib (Verzenio)—among patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer.

o Across the overall population, imlunestrant monotherapy improved PFS compared with standard endocrine therapy (HR, 0.87; 95% CI, 0.72-1.04; P = .12).

o Imlunestrant plus abemaciclib also showed a PFS improvement vs endocrine therapy across the overall population (HR, 0.57; 95% CI, 0.44-0.73; P <.001).

· Phase 2 SOLTI-VALENTINE Trial (NCT05569811)

o Patients with primary operable HR–positive/HER2-negative breast cancer were assigned to receive patritumab deruxtecan (HER3-DXd) alone, HER3-DXd plus letrozole (Femara), or standard multiagent chemotherapy.

o HER3-DXd monotherapy yielded a pathologic complete response (pCR) rate of 4.0% (95% CI, 0.5%-13.7%) and an objective response rate (ORR) of 70.0% (95% CI, 55.4%-82.1%); the respective rates in the chemotherapy arm were 4.2% (95% CI, 0.1%-21.1%) and 70.8% (95% CI, 48.9%-87.4%).

o Combining HER3-DXd with letrozole produced a pCR rate and ORR of 2.1% (95% CI, 0.1%-11.1%) and 81.3% (95% CI, 67.4%-91.1%), respectively.