Top Line: Should you start with a BRAF/MEK-targeted agent or an immune checkpoint inhibitor (ICI) for advanced, BRAF-mutated melanoma?
The Study: Preclinical studies have shown that BRAF-mutated melanoma cells can use the PD-1 axis to resist targeted therapy. So, maybe the answer is both. Here we have the preliminary results of IMspire150 where patients with BRAF V600E-mutated, advanced melanoma received vemurafenib (BRAF inhibitor) and cobimetinib (MEK inhibitor) with or without atezolizumab (ICI). The addition of atezo to targeted therapy significantly improved median progression-free survival (PFS) from >10 → >15 months based on investigator assessment. This was slightly less impressive on independent review of progression events (12 → 16 months). The improvement in PFS appears to have been driven by more durable response. In other words, overall response rates were similar, but the duration of response was much more prolonged with atezo (13 → 21 months). The difference in overall survival is still immature. Finally, the rate of grade 3+ toxicity was marginally higher with the triplet regimen.
TBL: Adding atezolizumab to combo BRAF/MEK-inhibition for BRAF V600-mutated melanoma improves progression-free survival. | Gutzmer, Lancet 2020


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