In 2024, several significant advancements in breast oncology were covered by Targeted Oncology^TM. Here are the top 10 developments from the year:

FDA Approval of Inavolisib for Advanced Breast Cancer: The FDA approved inavolisib (Itovebi, previously GDC-0077) plus palbociclib (Ibrance) and fulvestrant for the treatment of hormone receptor–positive (HR+), HER2-negative (HER2-), PIK3CA-mutated breast cancer. Inavolisib is a PI3K inhibitor for the treatment of advanced HR+/HER2- breast cancer with PIK3CA mutations and its designation is supported by data from the phase 3 INAVO120 study (NCT04191499). This approval offers a new targeted therapy option for patients with this specific genetic profile.

Ribociclib Approved for Early High-Risk Breast Cancer: Ribociclib (Kisqali), a CDK4/6 inhibitor, received FDA approval for use in combination with an aromatase inhibitor for the adjuvant treatment of HR+/HER2- early breast cancer at high risk of recurrence, including patients with node-negative disease. Data from the phase 3 NATALEE trial (NCT03701334) support this approval as the combination led to an improvement in invasive disease-free survival vs endocrine therapy alone in this patient population.

Olaparib Demonstrates Survival Benefit in Early Breast Cancer: Data from the phase 3 OlympiA trial (NCT02032823) showed that olaparib (Lynparza), a PARP inhibitor, significantly improved overall survival in patients with BRCA-mutated, HER2-negative early breast cancer. This marks the first PARP inhibitor to show such a benefit in this setting.

Precision Medicine Trial Improves Treatment by Tumor Subtype: The I-SPY 2.2 trial (NCT01042379) found that tailoring neoadjuvant therapy based on tumor subtype, including the use of antibody-drug conjugates and checkpoint inhibitors, improved outcomes in patients with early-stage breast cancer. Rebecca A. Shatsky, MD, I-SPY2.2 investigator and breast medical oncologist at the University of California San Diego Health, spoke with Targeted Oncology^TM to discuss the trial, its novel design, and its implications for the treatment of patients with breast cancer.

TNBC Cancer Vaccine Research: Ongoing research into vaccines aimed at preventing triple-negative breast cancer has shown promising early results. Specifically, the investigational breast cancer vaccine for triple-negative breast cancer (TNBC) showed encouraging results, with over 70% of patients exhibiting protocol-defined immune responses. These findings come from a phase 1 trial (NCT04674306) presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting.

FDA Approval of Tepylute for Breast and Ovarian Cancer: The FDA approved Tepylute (SH-105), a new formulation of an existing treatment, for use in patients with breast and ovarian adenocarcinoma. This approval provides an additional therapeutic option for these cancers.

Vepdegestrant Shows Clinical Activity in Combination Therapy: 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. In February 2024, the agent was granted fast track designation from the FDA as a monotherapy for the treatment of adult patients with ER+/HER2- locally advanced or metastatic breast cancer that received prior treatment with endocrine-based therapy.

Neoadjuvant/Adjuvant Pembrolizumab Improves Survival in Early-Stage TNBC: According to results from the phase 3 KEYNOTE-522 trial (NCT03036488) presented at the 2024 ESMO Congress, 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.

Can GLP-1 Agonists Impact Breast Cancer Care?Recent trends have placed GLP-1 receptor agonists, such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), at the forefront of discussions on general weight loss. During the 2024 American Society of Clinical Oncology Annual Meeting, several presentations highlighted the potential role of GLP-1 agonists in weight management for patients with breast cancer.

T-DXd Shows Survival Benefit in HR+/HER2-Low Breast Cancer: In the primary population of the phase 3 DESTINY-Breast06 trial (NCT04494425), which consisted of patients with HR+/HER2-low, metastatic breast cancer following 1 or more lines of endocrine therapy when treated with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd), a statistically significant and clinically meaningful improvement in progression-free survival was seen compared with those treated with standard-of-care chemotherapy.

These developments highlight the ongoing progress in breast oncology, with new therapies and strategies improving outcomes for patients across various stages and subtypes of breast cancer.