Applying Updated Breast Cancer Findings From ASCO to Clinical Practice

Following the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Neil M. Iyengar, MD, and Paolo Tarantino, MD, co-hosted a live X Space with CancerNetwork^® and discussed the latest trial updates that may impact clinical practice in the breast cancer field.

Iyengar is an associate attending physician at Memorial Sloan Kettering Cancer Center and a co-editor-in-chief of ONCOLOGY^®. Tarantino is a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School.

Iyengar and Tarantino discussed data regarding several trials and studies presented at the meeting. These presentations included:

• Phase 3 DESTINY-Breast06 Trial (NCT04494425)¹
  • Investigators evaluated treatment with trastuzumab deruxtecan (T-DXd; Enhertu) compared with investigator’s choice of chemotherapy among patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow metastatic breast cancer.
  • The median progression-free survival (PFS) was 13.2 months with T-DXd compared with 8.1 months in patients who received chemotherapy across the HER2-low population (HR, 0.62; 95% CI, 0.51-0.74; P <.0001).
  • Primary analysis overall survival (OS) data show favorable trends in the T-DXd arm across the HER2-low group (HR, 0.83; 95% CI, 0.66-1.05; P = .1181) and the intent-to-treat (ITT) population (HR, 0.81; 95% CI, 0.65-1.00). However, the OS data only reached 40% maturity at the time of the analysis.
• Phase 3 postMONARCH Study (NCT05169567)²
  • Patients with HR-positive, HER2-negative breast cancer and disease progression on CDK4/6 inhibitors and endocrine therapy were assigned to receive abemaciclib (Verzenio) or matched placebo plus fulvestrant (Faslodex).
  • The median PFS per investigator assessment was 5.6 months (95% CI, 5.4-9.2) with abemaciclib-based therapy vs 3.9 months (95% CI, 3.7-5.4) with placebo plus fulvestrant (HR, 0.66; 95% CI, 0.48-0.91; P = .01).
  • The investigator-assessed objective response rate (ORR) was 17% vs 7% in each respective arm.
• Phase 2 SACI-IO HR+ Trial (NCT04448886)³
  • Investigators assessed sacituzumab govitecan-hziy (Trodelvy) alone or in combination with pembrolizumab (Keytruda) for HR-positive, HER2-negative metastatic breast cancer regardless of PD-L1 status.
  • Combination therapy yielded a numerical improvement in median PFS (8.12 months; 95% CI, 4.51-11.12) compared with sacituzumab govitecan monotherapy (6.22 months; 95% CI, 3.85-8.68), although this improvement did not reach statistical significance (HR, 0.81; 95% CI, 0.51-1.28; P = .37).
  • Immature OS data presented at the meeting highlighted a median OS of 18.52 months (95% CI, 16.55-not applicable [NA]) vs 17.96 months (95% CI, 12.50-NA) in each respective arm (HR, 0.65; 95% CI, 0.33-1.28; P = .21).

References

1. Curigliano G, Hu X, Dent RA, et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): primary results from DESTINY-Breast06 (DB-06). J Clin Oncol. 2024;42(suppl 17):LBA1000. doi:10.1200/JCO.2024.42.17_suppl.LBA1000
2. Kalinsky K, Bianchini G, Hamilton EP, et al. Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: primary outcome of the phase 3 postMONARCH trial. J Clin Oncol. 2024;42(suppl 17):LBA1001. doi:10.1200/JCO.2024.42.17_suppl.LBA1001
3. Garrido-Castro A, Kim, SE, Desrosiers J, et al. SACI-IO HR+: a randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer. J Clin Oncol. 2024;42(suppl 17):LBA1004. doi:10.1200/JCO.2024.42.17_suppl.LBA1004