Aprepitant use during chemotherapy and association with survival in women with early breast cancer

Background Preclinical studies have shown that aprepitant, an antiemetic used to prevent chemotherapy-induced nausea and vomiting, slows mammary tumor growth and progression. Here, we evaluated the association between aprepitant and survival in a large cohort of women with early breast cancer. Methods Using linked nationwide registry data, we identified 13,811 women diagnosed with early breast cancer between 2008 and 2020 in Norway, who received chemotherapy and antiemetics. Women were followed for metastasis and death from one year after diagnosis until the end of 2021. To evaluate the association between aprepitant use and distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) we used Cox regression models, controlling for tumor and patient characteristics, chemotherapy regimens, and use of other antiemetics. Results During chemotherapy, 7,047 (51%) women were supplied with aprepitant. Overall, aprepitant use was associated with better DDFS (HRDDFS 0.89; 95%CI 0.79-1.00) and BCSS (HRBCSS 0.83; 95%CI 0.71-0.97). The survival advantage was specific to women with non-luminal breast cancer (HRDDFS 0.69; 95%CI 0.56-0.83; HRBCSS 0.64; 95%CI 0.51-0.81) and was strongest in women with triple negative breast cancer (TNBC)(HRDDFS 0.66; 95%CI 0.53-0.83; HRBCSS 0.61; 95%CI 0.47-0.80). In women with non-luminal breast cancer, longer durations of aprepitant use were associated with increasingly favorable survival outcomes (DDFS: Ptrend=0.002; BCSS: Ptrend=0.016). Supply of other antiemetics of different drug classes was not associated with survival. Conclusions Aprepitant use during chemotherapy treatment was associated with better prognosis for women with non-luminal early breast cancer, in particular TNBC. Long-term clinical trials are required to confirm these findings.