1137P - Treatment strategies and survival outcomes in a nationwide, population-based cohort of patients with melanoma brain metastases: The role of planned shift in systemic therapy and postoperative stereotactic radiotherapy

Background

Modern therapies have significantly improved outcome for patients with melanoma brain metastases (MBM). Still, the prognosis is poor, and the optimal treatment strategy is not well defined. Here, we report on the survival outcomes of systemic and locoregional treatments in an unselected, nationwide population-based cohort of patients with MBM.

Methods

All patients diagnosed with MBM in Denmark between 2015-2022 were retrospectively included. Patients were identified using the Danish Metastatic Melanoma Database (DAMMED) and local records of surgery and radiotherapy. Data were obtained from patient records.

Results

A total of 838 patients were included. Median overall survival (mOS) of the entire cohort was 9.0 months, and 112 patients were alive >3 years after diagnosis of MBM. Treatment with immune checkpoint inhibitors (ICI), ipilimumab + nivolumab, resulted in an intracranial overall response rate (icORR) of 46%, and a 2-year OS of 49% whereas BRAF/MEK-inhibitors (BRAF/MEKi) resulted in an icORR of 56%, and 2-year OS of 20%. A subgroup of patients with symptomatic MBM, treated initially with BRAF/MEKi with planned shift to ICI, had an icORR of 70%, 2-year OS of 50% and reached the longest mOS of 26 months. Patients with meningeal carcinomatosis (n=67) had a mOS of 8.4 months. Systemic therapy significantly improved OS for these patients, but no survival benefit was observed for patients receiving ICI compared to BRAF/MEKi. In total, 230 patients underwent surgery for MBM; of these, 30 received postoperative stereotactic radiosurgery (SRS). Baseline characteristics were balanced between the two groups. No benefit in OS or intracranial progression free survival was observed for patients receiving postoperative SRS.

Conclusions

Modern systemic therapies have improved survival for real-world patients with MBM; BRAF/MEKi had the highest icORR while ICI generated more durable responses. Planned shift from BRAF/MEKi to ICI can lead to long-term survival in selected patients. Postoperative SRS for patients undergoing surgery for MBM is questioned as a standard procedure.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

R.B. Friis: Non-Financial Interests, Personal, Other, Travel and conference expenses: MSD. M. Donia: Financial Interests, Personal, Invited Speaker, Teaching: Novartis, Roche; Financial Interests, Personal, Other, Advisor: Achilles Therapeutics; Non-Financial Interests, Other, Sub-investigator of clinical trial with connected translational research: Bristol Myers Squibb; Non-Financial Interests, Personal, Proprietary Information, Proprietary data access: Bristol Myers Squibb; Non-Financial Interests, Personal, Proprietary Information, Proprietary Data Access: Genentech; Other, Chairman of the Melanoma and Non-melanoma Skin Cancer Scientific Committee: Danish Medicines Council (Medicinrådet). C.A. Haslund: Financial Interests, Personal, Invited Speaker: MSD, GSK, BMS; Financial Interests, Institutional, Local PI: BMS, Tesaro, MSD, IO Biotech, Chimerix, Incyte; Financial Interests, Institutional, Coordinating PI: GSK, Celgene Aps. H. Schmidt: Other, Institutional, Other: Danish Medicines Council, Member of the Melanoma and Non-Melanoma Skin Cancer Scientific Committee. L. Bastholt: Non-Financial Interests, Advisory Role, Scientific committee under Danish Medicines Agency regarding new Treatments of Melanoma, Skin Cancer and Thyroid Cancer: Danish Medicines Agency. I. Svane: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre, Novartis, Roche, BMS; Financial Interests, Personal, Writing Engagement: MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder Warrants: IO Biotech; Financial Interests, Institutional, Research Grant: Adaptimmune, Enara Bio, Lytix Biopharma, TILT Biotherapeutics; Financial Interests, Institutional, Funding: Evaxion; Non-Financial Interests, Principal Investigator: BMS, Novartis, Roche, TILT Biotherapeutics, Lytix Biopharma. E. Ellebæk: Financial Interests, Personal, Invited Speaker: Pierre Fabre, BMS, Novartis, MSD, Pfizer; Other, Travel and conference expenses: MSD, Pierre Fabre. All other authors have declared no conflicts of interest.