Aprepitant, a commonly used antiemetic, led to improvements in patient outcomes when given during chemotherapy treatment for patients with non-luminal early breast cancer. Patients showed better prognoses and survival advantages, particularly among those with triple-negative breast cancer. Study findings were published in the Journal of the National Cancer Institute.
“Because of the nature of triple-negative breast cancer, there are fewer targeted treatment options, and therefore repurposing of drugs with well-established safety profiles is an attractive path for rapid translation to improve cancer treatment and outcomes,” stated senior study author Aeson Chang, PhD, Lecturer in Drug Discovery Biology at the Monash Institute of Pharmaceutical Sciences in Melbourne, Australia.
Study Methods and Rationale
Aprepitant is commonly prescribed for the prevention of chemotherapy-induced nausea and vomiting, but preclinical data have shown that it can also slow mammary tumor growth and progression.
“Very little is known about how and why aprepitant use could impact long-term survival outcomes in women with breast cancer, which is why we wanted to examine whether its use at the time of chemotherapy treatment may be linked with survival outcomes in a large population-based cohort of women with early-stage breast cancer,” Dr. Chang said.
In collaboration with the Norwegian Institute of Public Health, researchers analyzed data from the Cancer Registry of Norway for 13,811 women who were diagnosed with early breast cancer in Norway between 2008 and 2020. These women were prescribed antiemetics and chemotherapy. All of the patients were followed for metastasis and death through the end of 2021.
Key Study Findings and Significance
Of the selected women with early breast cancer, 51% received aprepitant. The antiemetic led to a reduced risk for distant disease–free survival (hazard ratio [HR] = 0.89; 95% confidence interval [CI] = 0.79–1.00) and breast cancer–specific survival (HR = 0.83; 95% CI = 0.71–0.97).
Only women with non-luminal disease showed such a survival advantage, in terms of a reduced distant disease–free survival risk (HR = 0.69; 95% CI = 0.56–0.83) and breast cancer–specific survival risk (HR = 0.64; 95% CI = 0.51–0.81). Women with triple-negative breast cancer showed the greatest potential benefit, with the risk for distant disease recurrence reduced by 34% (HR = 0.66; 95% CI = 0.53–0.83) and the risk for breast cancer–related death reduced by 39% (HR = 0.61; 95% CI = 0.47–0.80).
“Triple-negative breast cancer can be especially challenging to treat... new treatment pathways are important. We believe further studies are urgently needed to evaluate the effect of aprepitant in preventing cancer relapse and potentially inform new anti-nausea prescribing guidelines down the track,” stated co-senior study author Erica Sloan, PhD, Professor of Drug Discovery Biology at the Monash Institute of Pharmaceutical Sciences.
“Generally speaking, when aprepitant is taken, it’s during the first 3 days of chemotherapy treatment. Given the association between aprepitant and improved cancer outcomes uncovered in this study, it has led us to wonder if even greater survival would be observed if longer term use of aprepitant was factored into the patients' dosing schedule,” Dr. Chang said. Longer durations of aprepitant use were associated with even greater survival benefits in the study.
Different classes of antiemetics were not associated with survival benefit, the authors noted.
“This is a very exciting finding. Since this is the first observational study, further observational studies and clinical trials are required to confirm our findings in breast cancer and likely in other cancer types,” stated lead author Edoardo Botteri, PhD, Pharmacoepidemiologist at the Cancer Registry of Norway within the Norwegian Institute of Public Health. “Given what this study has uncovered, it’s essential these links are further explored—we now need to better understand why these associations have presented themselves and from there we can look at what this might mean for prescribing and dosing regimens in the future.”
Disclosure: For full disclosures of the study authors, visit academic.oup.com.
