Metronomic capecitabine maintenance therapy has been shown to be more effective compared with observation for patients with triple-negative breast cancer (TNBC), according to a study led by Zhongyu Yuan, MD. Results of the study have been presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program. In this interview with i3 Health, Dr. Yuan shares insights on treating TNBC and future directions in the TNBC treatment landscape.
What are the most challenging aspects of treating patients with TNBC?
Zhongyu Yuan, MD: To date, TNBC has the worst outcome among all subtypes of breast cancer, which results from a lack of available treatment options coupled with the aggressive biological behavior of the cancer; many patients with early TNBC will have their cancer recur soon after standard treatment. We have seen the success of additional maintenance of endocrine or HER2-targeted therapy in patients with hormone receptor-positive or HER2-overexpression early breast cancer. The challenge has been that there are no effective maintenance therapies to reduce the risk of relapse and death for early TNBC.
Can you comment on the significance of your findings?
Dr. Yuan: The results of the SYSUCC-001 trial showed that the addition of metronomic capecitabine maintenance after standard treatment for early TNBC could significantly improve disease-free survival (DFS). Patients randomly assigned to capecitabine maintenance had relative and absolute reductions in DFS events of 36% and 10%, respectively. The absolute benefit is comparable with that of endocrine therapy (absolute benefit of about 12%) and HER2-targeted therapy (absolute benefit of about 8%). The positive results of the present trial suggest a novel view that continuous maintenance therapy after standard treatment for TNBC might have a key role in reducing the risk of relapse.
What are the next steps for this research?
Dr. Yuan: In this study, the metronomic capecitabine administration was set as 650 mg/m2 twice daily continuously for 1 year, considering the toxicities and treatment compliance of capecitabine. One interesting finding is that, in the node-positive subgroup, the 5-year DFS in the capecitabine arm was numerically higher but not significantly improved compared with that in the observation arm. Whether 1 year of capecitabine therapy is insufficient for these high-risk patients remains to be explored, because the peak risk of recurrence for patients with TNBC is normally within 2 years.
How do you see the treatment landscape evolving in the coming years?
Dr. Yuan: Metronomic chemotherapy (MC) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Some classic chemotherapeutic drugs have been brought back to life with this "new bottle of old wine" of MC. In addition to developing new drugs, I think we should also focus on the reuse of old classic drugs. We're going to be thinking about novel combinations for these old and new agents. Many of us are interested to know if it would be effective to combine metronomic capecitabine with immunotherapy in early TNBC. We also wonder if we will be able to make metronomic capecitabine work beyond just triple-negative tumors. We are going to carry out trials to see if adding metronomic capecitabine to endocrine and targeted therapy will allow not only better activity of the combination but also potentially allow benefit of metronomic capecitabine beyond TNBC. I'm hopeful that many of the traditional agents will be brought back to life with new drug administrations.
Do you have any advice for community oncologists who treat this patient population?
Dr. Yuan: Metronomic capecitabine maintenance is a safe and effective method to bring significant benefits to patients with early TNBC, which is the true embodiment of the new concept in clinical practice. Old wine in a new bottle has a different flavor.
About Dr. Yuan
Zhongyu Yuan, MD, of the Department of Breast Oncology at Sun Yat-Sen University Cancer Center in Guangzhou, China, has published 40 articles on breast cancer topics. Dr. Yuan is also working on a project to discover tailored treatments for young women with breast cancer taking adjuvant therapy.
For More Information
Wang XI, Wang SS, Huang H, et al (2020). Phase III trial of metronomic capecitabine maintenance after standard treatment in operable triple-negative breast cancer (SYSUCC-001). J Clin Oncol (ASCO Virtual Scientific Program), 38(suppl_15). Abstract 507. DOI:101200/JCO.2020.38.15_suppl.507
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.
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