Dr Esteva on the monarchE and NATALEE Trials in HR+/HER2– Breast Cancer

Francisco J. Esteva, MD, PhD, interim chief, Division of Hematology/Oncology, chief, Breast Medical Oncology, Lenox Hill Hospital, director, Breast Medical Oncology, Northwell Health, discusses the phase 3 monarchE (NCT03155997) and NATALEE (NCT03701334) trials in patients with hormone receptor (HR)–positive/HER2-negative breast cancer.

Since the monarchE and NATALEE studies evaluated distinct patient populations, making a direct comparison between these populations challenging, Esteva begins. The monarchE trial focused on patients with high-risk disease, defined as those with 4 or more positive axillary lymph nodes or 1 to 3 positive axillary lymph nodes coupled with tumors of grade 3 or higher or those at least 5 cm in size, he adds. Additionally, this trial enrolled a subset of patients with 1 to 3 positive axillary lymph nodes who exhibited high Ki-67 levels, Esteva explains.

Conversely, the NATALEE study extended its scope to encompass patients with high-risk, node-negative breast cancer, he expands. Notably, this study demonstrated improvements in 3-year invasive disease-free survival with ribociclib plus endocrine therapy vs endocrine therapy alone. The NATALEE regimen has potential applications in both node-positive and higher-risk, node-negative disease in the adjuvant setting, Esteva emphasizes. However, the duration of follow-up in the NATALEE study is short, leaving aspects of these findings open to further investigation and evaluation, he says. 

Findings from the monarchE trial supported the March 2023 expansion of the abemaciclib FDA indication to include adult patients with HR-positive, HER2-negative, node-positive, early breast cancer. Abemaciclib appears to be the therapy of choice for patients with higher-risk disease, Esteva continues. However, ribociclib (Kisqali), which was investigated in the NATALEE trial, offers a treatment alternative for patients in this population, he says. Additional follow-up data from NATALEE may provide a more comprehensive understanding of the long-term benefits of ribociclib, as well as its safety profile. NATALEE and monarchE continue to shape the breast cancer treatment paradigm, and the findings from these trials may refine therapeutic strategies and improve outcomes for a diverse range of patients, Esteva concludes.