The year 2024 witnessed significant strides in breast cancer treatment, marked by FDA approvals, clinical trial successes, and innovative therapeutic strategies. These advancements span various subtypes and stages of the disease, offering new hope and improved outcomes for patients.
Targeted Therapies Expand Treatment Options
The FDA approved inavolisib (Itovebi), a PI3K inhibitor, for hormone receptor-positive (HR+), HER2-negative (HER2-), PIK3CA-mutated advanced breast cancer. This approval, in combination with palbociclib (Ibrance) and fulvestrant, is based on data from the phase 3 INAVO120 study (NCT04191499). This provides a new targeted option for patients with this specific genetic profile, addressing a critical unmet need in advanced breast cancer.
Ribociclib (Kisqali), a CDK4/6 inhibitor, also received FDA approval for adjuvant use in combination with an aromatase inhibitor for HR+/HER2- early breast cancer at high risk of recurrence, including node-negative disease. The phase 3 NATALEE trial (NCT03701334) supported this approval, demonstrating improved invasive disease-free survival compared to endocrine therapy alone.
PARP Inhibitor Shows Survival Benefit in Early Breast Cancer
Olaparib (Lynparza), a PARP inhibitor, demonstrated a significant overall survival improvement in patients with BRCA-mutated, HER2-negative early breast cancer, according to data from the phase 3 OlympiA trial (NCT02032823). This marks the first PARP inhibitor to show such a benefit in this setting, solidifying its role in the adjuvant treatment of high-risk early breast cancer.
Precision Medicine and Novel Approaches
The I-SPY 2.2 trial (NCT01042379) highlighted the benefits of tailoring neoadjuvant therapy based on tumor subtype, including the use of antibody-drug conjugates and checkpoint inhibitors, which improved outcomes in early-stage breast cancer. This approach underscores the importance of personalized treatment strategies in breast cancer management.
Research into vaccines for triple-negative breast cancer (TNBC) has also shown promising early results. An investigational vaccine demonstrated encouraging results in a phase 1 trial (NCT04674306), with over 70% of patients exhibiting protocol-defined immune responses. This highlights the potential for preventative strategies in this aggressive breast cancer subtype.
The FDA also approved Tepylute (SH-105), a new formulation of an existing treatment, for use in patients with breast and ovarian adenocarcinoma, providing an additional therapeutic option for these cancers.
Vepdegestrant and Combination Therapies
Early-phase clinical trials indicated that vepdegestrant (ARV-471), a novel selective estrogen receptor degrader, in combination with other agents, demonstrated clinical activity in patients with advanced breast cancer. The agent received fast track designation from the FDA as a monotherapy for ER+/HER2- locally advanced or metastatic breast cancer that received prior endocrine therapy.
Pembrolizumab Improves Survival in Early-Stage TNBC
Results from the phase 3 KEYNOTE-522 trial (NCT03036488), presented at the 2024 ESMO Congress, showed that patients with early-stage TNBC had statistically significant improvements in overall survival with neoadjuvant pembrolizumab (Keytruda) plus chemotherapy, followed by adjuvant pembrolizumab, compared with neoadjuvant chemotherapy plus placebo, followed by adjuvant placebo.
T-DXd Demonstrates Survival Benefit in HR+/HER2-Low Breast Cancer
In the primary population of the phase 3 DESTINY-Breast06 trial (NCT04494425), patients with HR+/HER2-low metastatic breast cancer who had received one or more lines of endocrine therapy, treatment with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) resulted in a statistically significant and clinically meaningful improvement in progression-free survival compared to standard-of-care chemotherapy.
