KEY TAKEAWAYS
- The study performed an exploratory biomarker analysis of immunophenotyping data from the ARTISTRY-1 clinical trial.
- The analysis suggests NK cell expansion as a potential predictive biomarker for nemvaleukin response in melanoma, requiring further validation.
The order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors and its effect on the development of brain metastases (BM) in patients with metastatic unresectable BRAFV600-mutant melanoma remains unclear.
In this SECOMBIT trial, Paolo A. Ascierto and the team aimed to investigate how the sequence of these treatments influences outcomes in this patient population.
They performed an inclusive analysis of patients without BM who were enrolled in this three-arm trial. Those in arm A received the BRAF/MEK inhibitors encorafenib and binimetinib until they experienced progressive disease, followed by immune checkpoint inhibitors ipilimumab and nivolumab.
In arm B, patients were treated with ipilimumab and nivolumab until progressive disease occurred, followed by encorafenib and binimetinib. Arm C consisted of patients receiving encorafenib and binimetinib for 8 weeks, followed by ipilimumab and nivolumab until progressive disease, after which they were retreated with encorafenib and binimetinib.
About BM, 23 out of 69 patients in arm A, 11 out of 69 in arm B, and 9 out of 68 in arm C were diagnosed during the trial. At a median follow-up of 56 months, the 60-month BM-free survival rates were 56% for arm A, 80% for arm B (hazard ratio [HR] vs. A: 0.40, 95% confidence interval [CI] 0.23 to 0.58), and 85% for arm C (HR vs. A: 0.35, 95% CI 0.16 to 0.76).
The study concluded that in patients with unresectable metastatic melanoma, the treatment sequence of immune checkpoint inhibition followed by BRAF/MEK inhibitors was associated with longer periods of new BM-free survival compared to the reverse sequence. Additionally, a regimen in which immune checkpoint inhibition was sandwiched between BRAF/MEK inhibition also appeared to offer protection against BM.
The trial was sponsored by the Fondazione Melanoma Onlus.
Source: https://pubmed.ncbi.nlm.nih.gov/39315864/
Clinical Trial: https://clinicaltrials.gov/study/NCT02631447
Ascierto PA, Mandalà M, Ferrucci PF, et al. (2024). “Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma.” NEJM Evid. 2024;3(10):EVIDoa2400087. doi:10.1056/EVIDoa2400087
