Editor's Note:
The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) has demonstrated significant activity in the treatment of in patients with advanced breast cancer (ABC), and as a result, it is widely used in clinical practice. At the recently held 46th San Antonio Breast Cancer Symposium (SABCS 2023), Professor Marta Vaz Batista from Doutor Fernando Fonseca EPE Hospital in Portugal presented a phase II study that evaluated the efficacy and safety of T-DXd in patients with a history of brain metastases (BM) and/or LMC, including those with HER2[+] and HER2-low ABC.
Oncology Frontier: Thank you for joining us. Could you please share the key results from DEBBRAH Study?
Dr. Marta Vaz Batista : Certainly. DEBBRAH is a phase 2 trial, an investigator-initiated trial, funded by METZIR and sponsored by AstraZeneca. We focused on cohort 5, comprising patients with cytologically confirmed Leptomeningeal carcinomatosis. In this study, we included seven patients with HER2-positive and HER2-low advanced breast cancer. The results revealed a noteworthy median overall survival of 13.3 months. It’s worth noting that, as of the data cutoff in April of this year, two patients were still undergoing treatment. Additionally, the median progression-free survival was 8.9 months, demonstrating positive outcomes.
Oncology Frontier: That’s impressive. Can you elaborate on the safety aspect?
Dr. Marta Vaz Batista: Certainly. Despite the trial’s small size, including only seven patients in this particular condition, we found no new safety warnings specific to the use of tucatinib. There were no cases of pneumonitis in this cohort, although some manageable cases were observed in other cohorts. Overall, the safety profile aligned with larger trials involving tucatinib.
Oncology Frontier: Moving on, which patients do you believe would benefit from T-DXd, and what advantages does it offer for those with Leptomeningeal carcinomatosis?
Dr. Marta Vaz Batista: While our focus here was on Leptomeningeal carcinomatosis patients, we’ve previously reported results on those with brain metastases. This trial included patients with stable brain metastases post-local therapy, progressing brain metastases post-local therapy, and untreated patients with certified HER2-positive or HER2-low status. The results were intriguing. For example, in cohort one, where stability after local therapy was assessed, we achieved the primary endpoint of PFS at 16 months. In other cohorts, we looked at overall response rates, finding them to be around 40 to 50%, consistent with studies like TUCATINIB. Notably, tucatinib showed efficacy both outside and within the brain, indicating its ability to penetrate and work in the central nervous system.
