Anti-Nausea Drug Aprepitant Shows Significant Survival Benefits in Triple-Negative Breast Cancer
核心洞察
A large observational study of 13,811 women with early-stage breast cancer (搜索) found that aprepitant, a commonly prescribed anti-nausea medication, was associated with an 11% lower risk of cancer recurrence and 17% lower risk of breast cancer-related death.
The survival benefits were particularly pronounced in triple-negative breast cancer (搜索) patients, showing a 34% reduced risk of metastasis and 39% lower risk of death from breast cancer.
The findings suggest potential for repurposing aprepitant as a cancer therapy beyond its traditional use for chemotherapy-induced nausea and vomiting prevention.
A commonly prescribed anti-nausea medication used during chemotherapy has demonstrated significant survival benefits for women with early-stage breast cancer (搜索), particularly those with the aggressive triple-negative subtype, according to a large observational study published in the Journal of the National Cancer Institute.
The research, co-led by Monash University and the Norwegian Institute of Public Health (搜索), analyzed Cancer Registry of Norway (搜索) data from 13,811 women diagnosed with invasive early-stage breast cancer (搜索) between 2008 and 2020. All participants received both chemotherapy and anti-nausea medications to prevent chemotherapy-induced nausea and vomiting.
Significant Survival Improvements Across Patient Population
The study found that women who used aprepitant during chemotherapy treatment experienced an overall 11% lower risk of developing cancer recurrence and 17% lower risk of breast cancer-related death during the 10-year follow-up period. Notably, when researchers examined other classes of anti-nausea medications, they found no association with improved cancer outcomes.
"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 (搜索)," said Dr. Aeson Chang from the Monash Institute of Pharmaceutical Sciences (MIPS).
Dramatic Benefits for Triple-Negative Breast Cancer
The most striking results emerged when researchers analyzed breast cancer subtypes. Women with triple-negative breast cancer (搜索) (TNBC) showed the greatest benefit, with aprepitant use associated with a 34% reduced risk of cancer recurrence and 39% reduced risk of death from breast cancer.
Triple-negative breast cancer (搜索), which accounts for about 10% to 15% of all breast cancers, lacks the three most common receptors found in most breast cancers: estrogen receptor (搜索) (ER), progesterone receptor (搜索) (PR), and HER2 (搜索). This aggressive form tends to grow and spread faster than other types and has fewer targeted treatment options.
"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," Dr. Chang explained.
Mechanism and Dosing Considerations
Aprepitant belongs to a class of drugs called neurokinin 1 receptor (搜索) (NK1R (搜索)) antagonists. It works by blocking the actions of signaling molecules in the brain called substance P neurokinins, which cause nausea and vomiting. Previous studies have implicated substance P and the NK1R system in breast cancer progression.
The study revealed a dose-response relationship, with longer aprepitant use associated with more favorable outcomes. Use for 12 days produced up to a 42% reduction in the risk of cancer recurrence or death from breast cancer.
"Generally speaking, when aprepitant is taken it's during the first three 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 patient's dosing schedule," Dr. Chang noted.
Clinical Implications and Future Research
The researchers found that the survival benefits were not statistically significant in hormone-receptor-positive (luminal) breast cancers, which are characterized by the presence of ER or PR on cancer cells. Non-luminal types, including HER2 (搜索)-positive and particularly triple-negative breast cancer (搜索), showed the greatest benefit.
Co-senior author Professor Erica Sloan, also from MIPS, emphasized the clinical significance: "Triple negative breast cancer can be especially challenging to treat and with around 3,000 new cases diagnosed each year in Australia, 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."
Current Treatment Context
Chemotherapy-induced nausea and vomiting affects up to 60% of early-stage breast cancer (搜索) patients receiving systemic chemotherapy. Recent guidelines recommend aprepitant use only in patients treated with chemotherapy highly likely to induce vomiting and nausea.
Dr. Chang suggested that the findings warrant exploration of expanding aprepitant use as a routine antiemetic regimen during chemotherapy treatment.
Study Limitations and Next Steps
The study's first author, Dr. Edoardo Botteri, a pharmacoepidemiologist at the Cancer Registry of Norway (搜索), acknowledged the observational nature of the research: "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."
The researchers noted several limitations, including that aprepitant users were more likely to receive intensive chemotherapy regimens, and that filling a prescription doesn't guarantee the drug was actually taken. As an observational study, it cannot prove cause and effect.
"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," Dr. Botteri concluded.