Adding Aprepitant to Chemo Extends Non-Luminal Breast Cancer Survival

Patients with luminal breast cancers who took aprepitant for more than 12 days had the best survival outcomes.

The addition of the antiemetic aprepitant (Emend) to standard chemotherapy was linked to improved survival outcomes for patients with early non-luminal breast cancers, particularly those with triple-negative breast cancer, according to data published in the Journal of the National Cancer Institute.¹

Stratified analyses demonstrated a significant improvement in distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) for patients with non-luminal cancers taking aprepitant vs those not taking aprepitant.

Patients with non-luminal breast cancer who took aprepitant experienced a 31% reduction in the risk of metastasis or death (hazard ratio [HR], 0.69; 95% CI, 0.56-0.83; P < .001) and a 36% reduction in the risk of breast cancer progression or death (HR, 0.64; 95% CI, 0.51-0.81; P < .001).

However, patients with luminal cancers did not experience a significant benefit. The hazard ratios for DDFS and BCSS were 0.98 (95% CI, 0.85-1.13; P = .808) and 1.03 (95% CI, 0.85-1.25; P = .780), respectively, in patients with luminal breast cancers.

Luminal breast cancers are characterized by hormone receptor (HR) positivity along with any of three combinations: HER2 negativity and low expression of cell proliferation marker Ki-67, HER2 positivity and higher Ki-67 expression, or HER2 negativity and higher Ki-67 expression.^1,2 Non-luminal breast cancer is usually HR-negative and may or may not be HER2 positive.

With a median follow-up of 5.2 years, the use of aprepitant in the patient population overall was associated with a statistically significant 11% reduction in risk of death or metastasis (HR, 0.89; 95% CI, 0.79-1.00; P = .47) and a non-statistically significant 17% reduction in death or breast cancer progression (HR, 0.83; 95% CI, 0.71-0.97; P = .20) in patients with breast cancer who were treated with aprepitant vs those treated with an antiemetic regimen that did not include aprepitant.

Which patients benefited the most from the addition of aprepitant?

Patients with triple negative breast cancer (TNBC) had the greatest survival benefit from aprepitant use. For that patient population, the risk of metastasis or death was reduced by 34% (HR, 0.66, 95% CI, 0.53-0.83; P = .021), and the risk of breast cancer progression or death was reduced by 39% (HR, 0.61; 95% CI, 0.47-0.80; P < .001).

Additionally, aprepitant was associated with longer survival at higher rates in patients 55 years and older compared with younger patients. Those 55 and older experienced a 23% reduction in risk of metastasis or death (HR, 0.77, 95% CI, 0.66-0.89; P = .34) and a 31% reduction in the risk of breast cancer progression or death (HR, 0.69; 95% CI, 0.56-0.85; P < .001).

Of note, patients with non-luminal disease saw the greatest benefit when using aprepitant for more than 12 days. Use of aprepitant reduced risk of metastasis or death and risk of breast cancer progression or death by 45% (HR, 0.54; 95% CI, 0.39-0.75; P = .002) and 39% (HR, 0.61; 95% CI, 0.42-0.88; P = .016), respectively, in patients with non-luminal disease, whereas no such trend was observed in patients with luminal disease.

Who was included in the study?

The study observed all women diagnosed with invasive breast carcinoma from 2008 to 2020 in Norway, excluding patients diagnosed with another cancer or who developed metastases before or up to 1 year after breast cancer diagnosis, those with stage IV or unknown stage cancer, those not receiving chemotherapy, and those not receiving an antiemetic, yielding a population of 13,811 evaluable patients.

Among evaluable patients, 7,047 received aprepitant, and 6,764 did not, with patient and disease characteristics evenly distributed between the two groups.

Reference

1. Botteri E, Hjorth S, Conforti F, et al. Aprepitant use during chemotherapy and association with survival in women with early breast cancer. J Natl Cancer Inst. Published online July 14, 2025. doi:10.1093/jnci/djaf178
2. Orrantia-Borunda E, Anchondo-Nuñez P, Acuña-Aguilar LE, et al. Subtypes of Breast Cancer. In: Mayrovitz HN, editor. Breast Cancer [Internet]. Exon Publications; 2022. doi: 10.36255/exon-publications-breast-cancer-subtypes