Anthracyclines and paclitaxel are the basis of chemotherapy for breast cancer, but many patients with advanced disease are clinically resistant to both, which presents a major dilemma for physicians.
Eribulin, a chemotherapy drug launched in the United States in 2010 November 2010, is approved for use in patients with metastatic breast cancer who have used two prior chemotherapy regimens. Although the drug is still under review for approval, it is likely to be one of the new treatment options for domestic patients with metastatic breast cancer in the future.
How does eribulin work?
Ezhimbulin is a non-paclitaxel microtubule inhibitor. Microtubules play an important role in cell division as cells undergo a continuous cycle of cell division and proliferation. Eribulin interferes with cell division by inhibiting the action of microtubules, thereby blocking the proliferation of cancer cells and inhibiting tumor growth.
The kinetic inhibition of microtubules by eribulin has a unique mechanism that allows breast cancer to potentially respond therapeutically to eribulin even after it has been resistant to multiple chemotherapeutic agents.
Is eribulin still effective after failure of multiple chemotherapies in advanced breast cancer?
For patients with locally advanced or metastatic breast cancer who have been treated with anthracyclines/paclitaxel and capecitabine, a phase II study showed an objective remission rate of nearly 10% with a general overall survival time of 10.4 months for switching to eribulin, with about 17% of patients able to benefit. Approximately 54% of patients on eribulin therapy had moderate (grade 3 to 4 neutropenia).
Are there more detailed studies confirming the efficacy of eribulin alone?
The phase III clinical study called EMBRACE enrolled 762 patients with advanced breast cancer who had received 2 to 5 prior chemotherapy regimens. From the results, compared to other treatments, eribulin prolonged overall survival by 2.5 months (13.1 months and 10.6 months, respectively), reduced the 1 year risk of death by 19% , and improved remission rates.
EMBRACE In the study, the main moderate adverse effects of eribulin were weakness and fatigue, neutropenia, and peripheral neuropathy. Based on this study, eribulin was FDA approved for the treatment of metastatic breast cancer that has received at least two chemotherapy regimens (containing anthracycline and paclitaxel-based chemotherapy drugs).
Another phase III clinical study enrolled 1102 patients with locally progressive or metastatic breast cancer who also had failed multiple chemotherapies before choosing eribulin. Overall, eribulin did not result in an increased survival benefit.
But further analysis found that in HER2-negative and triple-negative breast cancers, eribulin prolonged survival compared with capecitabine. The benefit was particularly pronounced in triple-negative patients, with patients surviving about 5 months longer (median overall survival 14.4 months, 9.4 months).
Currently, eribulin is one of the single-agent chemotherapy regimens recommended by the National Comprehensive Cancer Network (NCCN) guidelines for advanced breast cancer.
Landing in China is on the horizon
More applications for eribulin are being explored, including combination with other treatments for more inflammatory breast cancers.
A domestic phase III clinical study comparing eribulin and vinorelbine for the treatment of locally recurrent or metastatic breast cancer (No. CTE20130252) is ongoing and requires patients who have received at least 2 chemotherapeutic agents, including anthracyclines and paclitaxel drugs. The study has now completed patient recruitment, and results are not yet available.
Summary
For patients with anthracycline- and paclitaxel-resistant metastatic breast cancer who have failed multiple lines of therapy, consider eribulin monotherapy, which has the potential to extend overall survival by 2.5 months compared with other chemotherapy. Related studies are also underway in China, and the results may lead to the introduction of eribulin in this country.