Fam-Trastuzumab Deruxtecan Shows Positive Results for HER2-Positive Breast Cancer with Brain Metastases

Fam-trastuzumab deruxtecan-nxki (Enhertu: AstraZeneca) achieved a 61.6% progression-free survival (PFS) at 1 year in patients with HER2-positive metastatic breast cancer (BC) who have brain metastases (BMs). The results from the phase 3b/4 DESTINY-Breast12 trial (NCT04739761), presented at the European Society of Hematologic Oncology 2024 Congress, pave the way for advanced treatment of active and stable brain tumors.¹

In patients with BMs at baseline, the data showed a 12-month PFS of 61.6%. Image Credit: © tongpatong - stock.adobe.com

BC is one of the most commonly diagnosed type of cancer, accounting for approximately 30% of all new cases and affecting an estimated 310,000 women in the US in 2024. Due to increased screenings and BC education, most cases are diagnosed at the localized stage when the disease is easiest to treat. However, in some cases, the cancer metastasizes to the brain, commonly referred to as "secondary breast cancer in the brain." Younger women under the age of 35 have an increased risk of developing brain tumors, as well as patients with aggressive types of breast cancer, including HER2-positive BC.^2,3

“Up to [50%] of patients with HER2-positive metastatic breast cancer experience the spread of disease to the brain during the course of their illness, which significantly impacts quality of life and outcomes. These data help further characterize the clinical benefit and safety profile of [fam-trastuzumab deruxtecan-nxki] in these patients, which will help guide treatment decisions,” Nancy Lin, MD, associate chief of the division of breast oncology at Dana-Farber Cancer Institute, said in a news release.⁴

In the open-label, multicenter, international DESTINY-Breast12 study, researchers evaluated the safety and efficacy of fam-trastuzumab deruxtecan-nxki in patients with HER2-positive metastatic breast cancer who have BMs. The trial involved 504 patients (stable/active BMs [n = 263] and no BMs [n = 241]) treated with 1 or more prior anti-HER2–based regimens.^4,5

Primary end points were PFS in the BM cohort and objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors version 1.1 in the non-BM cohort. Secondary end points included central nervous system (CNS) PFS, ORR, time to second progression, CNS ORR (BMs cohort), incidence of new symptomatic CNS metastases (non-BMs cohort), time to progression, duration of response, overall survival, and safety (both cohorts).⁵

In patients with BMs at baseline, the data showed a 12-month PFS of 61.6% (95% confidence interval (CI): 54.9–67.6) and a 12-month CNS PFS of 58.9% (95% CI: 51.9–65.3), which was consistent patients with both active and stable tumors. Additionally, the researchers observed a 12-month PFS rate of 62.9% and a 12-month CNS PFS rate of 57.8% in patients with stable BMs, with similar percentages for patients with active BMs. In patients without BMs at baseline, the primary end point of confirmed an ORR of 62.7% with 23 complete responses and 128 partial responses.⁵

In a post-hoc analysis, patients with active BMs who had not received prior local CNS therapy showed a better CNS ORR (82.6%; n=19/23) compared with those who had progressed (50%; n=19/38), indicating the increased benefit of fam-trastuzumab deruxtecan-nxki in earlier lines.⁵

“Treating brain metastases in patients with breast cancer is challenging as there are few effective treatment options,” Mark Rutstein, global head of oncology development at Daiichi Sankyo, said in a news release. “Building on previous studies, these results show [fam-trastuzumab deruxtecan-nxki] can provide strong overall and intracranial clinical activity and support its potential role in treating patients with active or stable brain metastases.”⁴

REFERENCES

1. A study of t-dxd in participants with or without brain metastasis who have previously treated advanced or metastatic her2 positive breast cancer (destiny-b12). ClinicalTrials.gov Identifier: NCT04739761. Updated July 19, 2024. Accessed September 18, 2024. https://clinicaltrials.gov/study/NCT04739761

2. Breast cancer facts and statistics. Breastcancer.org. July 30, 2024. Accessed September 19, 2024. https://www.breastcancer.org/facts-statistics

3. Breast cancer metastasis to the brain. Moffitt Cancer Center. Accessed September 19, 2024. https://www.moffitt.org/cancers/brain-tumor/brain-metastases/breast/#:~:text=Breast%20cancer%20sometimes%20metastasizes%20(spreads,with%20stage%204%20breast%20cancer

4. Enhertu® (fam-trastuzumab deruxtecan-nxki) showed substantial clinical activity in patients with her2-positive metastatic breast cancer and brain metastases. AstaZeneca. September 13, 2024. Accessed September 18, 2024. https://www.astrazeneca-us.com/media/press-releases/2024/enhertur-fam-trastuzumab-deruxtecan-nxki-showed-substantial-clinical-activity-in-patients-with-her2-positive-metastatic-breast-cancer-and-brain-metastases.html

5. Harbeck N, Ciruelos E, Jerusalem G, et al. Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial. Nat Med. September 13, 2024. doi:10.1038/s41591-024-03261-7