Tumors of the central nervous system (CNS) represent one of the most critical challenges in clinical oncology. Among these, brain metastasis (BMs), where cancer cells spread from the primary tumor to the brain, are particularly difficult to treat. The unique environment of the CNS, along with the protective blood-brain barrier that restricts drug delivery, makes BMs resistant to conventional therapies, often resulting in a poor prognosis and limited treatment options. Another crucial challenge is leptomeningeal disease (LMD), a rare condition where cancer cells infiltrate the cerebrospinal fluid and the membranes surrounding the brain and spinal cord. Although LMD is less common, its incidence is rising as cancer patients live longer. Unfortunately, there is no specific approved treatment for LMD, and no consensus exists on how to manage this serious complication.
This difficult scenario is further compounded by the frequent exclusion of patients with BMs and LMD from clinical trials, leaving uncertainty about the potential benefits of new treatments for these patients. The recent SNO/ASCO CNS Metastases Conference, held August 8–10th, 2024, in Denver, Colorado, focused on the urgent unmet need for innovative therapies against BMs and LMD.
A platform for collaboration and networking
Jointly organized by the Society for Neuro-Oncology (SNO) and the American Society of Clinical Oncology (ASCO), the conference brought together clinicians, researchers, and industry partners under the theme "Leveraging Multi-Sector Collaboration to Disrupt CNS Metastases." The event emphasized the importance of overcoming barriers to therapeutic progress by fostering meaningful collaborations between all stakeholders and providing an invaluable platform for sharing knowledge and networking. Sessions covered a broad spectrum of topics, from basic and translational research to clinical practices, including radiation therapy, surgery, chemotherapy, targeted therapy, immunotherapy, and clinical trials.
Presentation spotlight: the DEBBRAH study
During these sessions, MEDSIR presented the final results of the DEBBRAH study, which evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate, in HER2-positive and HER2-low advanced breast cancer (ABC) patients with BMs and/or LMC. T-DXd had previously shown promising intracranial and extracranial efficacy in different clinical trials, but data specifically on active BMs as well as HER2-low ABC with BMs was limited.
Briefly, the DEBBRAH study enrolled 41 patients from 18 hospitals in Spain and Portugal, divided into 5 cohorts based on tumor and metastasis characteristics:
· Cohort 1: HER2-positive ABC with non-progressing BMs after radiotherapy and/or surgery.
· Cohort 2: HER2-positive or HER2-low ABC with asymptomatic untreated BMs.
· Cohort 3: HER2-positive ABC with progressing BMs after local treatment.
· Cohort 4: HER2-low ABC with progressing BMs after local treatment.
· Cohort 5: HER2-positive or HER2-low ABC and pathologically confirmed LMC.
The results, presented during the poster session, are particularly impressive. Cohort 1 showed a 16-week progression-free survival rate of 87.5%. Intracranial overall response rates in Cohorts 2, 3, and 4 ranged from 50% to 70%. Notably, Cohort 5 reported a median overall survival of 13.3 months. Download here the poster for more information.
These findings underscore the groundbreaking nature of this study. By including patients with untreated or progressing BMs and LMC, the DEBBRAH trial not only starts filling a critical gap in clinical research but also reinforces the importance of including these patient populations in future trials.
The SNO/ASCO CNS Metastases Conference was a unique opportunity to share our findings, collaborate with other experts, and contribute to the global effort against CNS tumors. We are incredibly proud of our participation, and we would like to especially thank Eileen Shimizu, PhD, Scientific Communications Expert at MEDSIR, for her exceptional presentation of the DEBRRAH study to the scientific community.
For those seeking a deeper understanding of the DEBBRAH study, our published article in Neuro-Oncology details the outcomes for Cohorts 1, 2, and 3, which demonstrated T-DXd’s efficacy in HER2-positive ABC with progressing BMs for the first time. We are also thrilled to announce that the results from Cohorts 2 and 4 and the results from Cohort 5 have been recently accepted for publication in ESMO Open and Med journals, respectively. Stay tuned for these upcoming publications, and in the meantime, explore our previous contributions to scientific events with more insights here and here!
At MEDSIR we are committed to advancing the fight against cancer, one breakthrough at a time!
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