Addressing Patient Subgroups Is a Key Topic During Breast Cancer Conference

Targeted Therapies in Oncology, January 2023, Volume 11, Issue 17
Pages: 55

Recent updates to clinical care for patients with ER-positive disease include the emergence of breast cancer subtypes, oral selective estrogen receptor degraders, and other oral targeted therapies.

The emergence of breast cancer subtypes and novel management approaches in ER-positive disease, including oral selective estrogen receptor degraders and other oral targeted therapies, place a greater emphasis on multidisciplinary care for these patients. Kevin Kalinsky, MD, MS, a member of the steering committee of the 40th Annual Miami Breast Cancer Conference®, spoke with Targeted Therapies in Oncology™ about the conference and the most recent updates to clinical care.

The in-person conference being held in Miami Beach, Florida, will kick off with 3 tumor board discussions on March 2, 2023, and during the next 2 days will focus on surgical, medical, radiation oncology, and nursing topics. In addition to learning about the latest data, attendees will hear from national and international experts in the field about their experiences treating the disease.

“This conference doesn’t shy away from...real-life controversies and present[s] data that will...inform clinical decisions,” Kalinsky said. “After attending the Miami Breast Cancer Conference®, physicians will walk away with a much better understanding of how to treat their patients with breast cancer.”

Recent Updates

Kalinsky, an associate professor at Emory University School of Medicine and chair of Breast Cancer Research at the Winship Cancer Institute, both in Atlanta, Georgia, noted that “immunotherapy for...metastatic triple negative breast cancer has been a game changer for about 14% of patients.”

Findings from KEYNOTE-355 (NCT02819518), which evaluated the addition of pembrolizumab (Keytruda) to chemotherapy, showed longer progression-free survival (PFS) than chemotherapy alone in patients with advanced triple negative breast cancer whose tumors expressed PD-L1 with a combined positive score (CPS) of 10 or greater.1

During the trial, 847 patients were randomly assigned to receive pembrolizumab plus chemo-therapy (n = 566) or placebo plus chemotherapy (n = 281). After 44.1 months, the median overall survival (OS) was 23.0 months in the pembrolizumab plus chemotherapy arm and 16.1 months in the placebo arm (HR for death, 0.73; 95% CI, 0.55-0.95; P = .1125). Median OS also favored the treatment arm: 17.2 vs 15.5 months, respectively (HR, 0.89; 95% CI, 0.76-1.05).

Disease Subtypes

Kalinsky looked to the 2022 San Antonio Breast Cancer Symposium (SABCS) held on December 6-10, 2022, pointing to findings from the phase 3 EMERALD trial (NCT03778931). Results demonstrated improvement in PFS with elacestrant compared with standard-of-care (SOC) endocrine therapy in patients with ER-positive/HER-2-negative metastatic breast cancer who had been previously treated with CDK4/6 inhibitors.2 Results showed that the length of prior treatment with CDK4/6 inhibitors was associated with longer PFS.

Patients were randomly assigned to receive either 400 mg of elacestrant daily (n = 239) or SOC endocrine therapy (n = 239) consisting of either fulvestrant (Faslodex), anastrozole (Arimidex), letrozole (Femara), or exemestane (Aromasin). In the elacestrant arm, 48% (n = 115) of patients had an ESR1 mutation, and in the control arm 47% (n = 113) had an ESR1 mutation.

In patients who had received CDK4/6 inhibitors for 6 months, investigators reported a 31.2% increase in PFS compared with SOC (HR, 0.688). The median PFS for patients in this group was 2.79 months in the treatment arm vs 1.91 months in the control arm. After receiving CDK4/6 inhibitors for 12 months, patients in the treatment arm experienced a 38.7% increase in PFS compared with patients in the SOC arm (HR, 0.613). The median PFS for the patients in this group was 3.78 vs 1.91 months, respectively.

Among patients with an ESR1 mutation who had undergone at least 6 months of treatment with CDK4/6 inhibitors (92.3%), those receiving elacestrant experienced a 48.3% increase in PFS compared with those receiving SOC (HR, 0.517). The median PFS in this group was 4.14 months for patients on elacestrant vs 1.87 months for those on SOC.

For patients with ESR1-mutant disease who had undergone 12 months or more of CDK4/6 inhibitor treatment (71.6%), those who received elacestrant saw a 59% increase in PFS compared with those receiving SOC (HR, 0.410). The median PFS for patients in this group was 8.61 months in the treatment arm and 1.91 months in the control arm.

Another study discussed during SABCS, the phase 2 SERENA study (NCT04214288), evaluated patients who were ER-positive/HER2-negative.3 They received 2 monotherapy doses of camizestrant vs SOC fulvestrant (Faslodex). Investigators noted that PFS more than doubled in patients in the treatment arm vs those in the control.

The study comprised 3 treatment arms—300 mg (n = 20), 75 mg (n = 74), and 150 mg (n = 73) of camizestrant—and a fulvestrant cohort (n = 173). With a median follow-up of 16.6 months, 16.6 months, and 17.4 months in the 75-mg, 150-mg, and fulvestrant groups, respectively, the median PFS was 7.2 months (95% CI, 3.7-10.9; HR, 0.58; 95% CI, 0.41-0.81; P = .0124), 7.7 months (95% CI, 5.5-12.9; HR, 0.67; 95% CI, 0.48-0.92; P = .0161), and 3.7 months (95% CI, 2.0-6.0).

PFS was also determined in other sub-groups of SERENA. Among patients who had previously received a CDK4/6 inhibitor, the median PFS was 5.5 months (95% CI, 3.7-10.9; HR, 0.49; 95% CI, 0.31-0.75) and 3.8 months (HR, 0.68; 95% CI, 0.44-1.04) in the 75-mg and 150-mg camizestrant dose cohorts, respectively, and 2.1 months (95% CI, 1.9-3.7) in the fulvestrant arm.

Addressing patient subgroups is a significant challenge in breast cancer, “and it’s an emerging topic that I’m sure we’ll be hearing updates about throughout [the conference],” Kalinsky said.

1. Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217-226. doi:10.1056/NEJMoa2202809
2. Bardia A, Bidard FC, Neven P, et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2- metastatic breast cancer: updated results by duration of prior CDK4/6i in metastatic setting. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS3-01. Accessed December 15, 2022.
3. Oliveira M, Pominchuk D, Nowecki Z, et al. Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: results of the randomized, multi-dose Phase 2 SERENA-2 trial. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS3-02. Accessed December 15, 2022. h ps://