Editor's Note: At the 2024 European Society for Medical Oncology (ESMO) Annual Congress, Dr. Hitomi Sakai from the Advanced Cancer Translational Research Institute in Japan reported on the significant efficacy of the OLZ-based triple therapy in preventing treatment-related nausea and vomiting (NV) in patients treated with T-DXd, providing an important reference for clinical practice. After the conference, Dr. Hitomi Sakai was interviewed by Oncology Frontier, where she introduced the research process and related results.

Oncology Frontier：Nausea and vomiting are common adverse reactions in the treatment of patients. What specific effects do you think of nausea and vomiting on the quality of life of patients?

Dr. Hitomi Sakai: Thank you so much for having me this time. Mostly, nausea and vomiting induced by trastuzumab deruxtecan is low-grade, but even low-grade nausea and vomiting can impair patients’ quality of life if it lasts long. So management of nausea and vomiting is really important.

Dr. Hitomi Sakai: In the current study, a patient took olanzapine at 5mg after evening meal or bedtime from day 1 to day 6 in addition to serotonin type 3 receptor antagonists and dexamethasone. We chose 5mg olanzapine. The reason we chose 5mg dose is considering toxicity. In the prophylactic setting, severe somnolence or sedation induced by olanzapine would be unacceptable. In Japan, 5mg dose is commonly prescribed based on the phase III study performed by Dr. Hashimoto. So we adopted 5mg dose in the current study.

Oncology Frontier：What are the unique advantages of the olanzapine based triple antiemetic regimen in this study compared with other commonly used antiemetic drugs? Is it possible to become the standard antiemetic regimen for T-DXd treatment in the future?

Dr. Hitomi Sakai: In the current study, we defined from 120 hours to 504 hours after T-DXd administration as a persistent phase to evaluate patient’s persistent symptoms for the first time. In the current study, the efficacy of olanzapine was observed not only in the delayed phase, 24 to 120 hours, but also in persistent phase. We believe olanzapine is better in preventing nausea and vomiting induced by T-DXd. It appears to be a good treatment choice in patients receiving T-DXd, but we need to confirm in future phase III study.

Oncology Frontier：What outlook or suggestions do you have for the future application of T-DXd in breast cancer treatment? In particular, how to better manage its side effects to improve the patient’s treatment experience and prognosis?

Dr. Hitomi Sakai: A lot of clinical studies using T-DXd is ongoing in early setting for primary breast cancer and if T-DXd is administered in earlier setting, treatment duration of T-DXd can be less long, so managing side effects is getting more and more important. It’s wonderful that new cancer agent prolongs patient survival, but patients are now enduring side effects for longer period of time, so we need to improve managing side effects more and more.