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PD-1, BRAF/MEK inhibitors extend survival in BRAF-mutated melanoma
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PD-1 inhibitors, as well as BRAF and MEK inhibitors, prolonged OS in advanced BRAF–mutated melanoma compared with other treatments, according to results of a meta-analysis.
“Targeted therapies, including selective BRAF and MEK inhibitors, have drastically improved rates of PFS and OS in patients with metastatic melanoma harboring a BRAF V600 mutation,” Tahira Devji, BSc, PhD candidate in health research methodology and clinical epidemiology at McMaster University in Canada, and colleagues wrote. “Immune checkpoint inhibitors have also shown significant benefit over conventional chemotherapies in randomized trials, regardless of BRAF mutation status.
“Thus, in the case of advanced BRAF–mutated melanoma, multiple effective first-line treatment options are available,” Devji and colleagues added. “No head-to-head randomized trials of targeted agents and immunotherapies have been conducted and, thus, the optimal treatment is unknown.”
The researchers analyzed 16 articles about 15 phase 2 or phase 3 randomized controlled trials published through April 29 (n = 6,662). Each study included at least one targeted inhibitor (BRAF or MEK) or an immune checkpoint inhibitor (CTLA-4 or PD-1).
PD-1 inhibitors and BRAF/MEK inhibitors appeared associated with longer OS than all treatments except CTLA-4/granulocyte-macrophage colony–stimulating factor.
Researchers reported no significant difference in OS between PD-1 and BRAF/MEK inhibitors (HR = 1.02; 95% CI, 0.72-1.45). Combined BRAF and MEK treatments were associated with a higher objective response rate (OR = 2; 95% CI, 1.64-2.45) than BRAF inhibition alone; however, both produced a higher objective response rate than other treatments. BRAF/MEK inhibition also was associated with longer PFS than all other treatments.
Eight studies included in the meta-analysis reported grade 3 or higher adverse events.
PD-1 therapy and chemotherapy appeared associated with the lowest risk for serious adverse events, with no significant difference between the two (OR = 1; 95% CI, 0.74-1.34). CTLA-4/PD-1 combined appeared associated with a higher risk for serious adverse events than CTLA-4 alone (OR = 1.63; 95% CI, 1.19-2.26) or PD-1 alone (OR = 2.99; 95% CI, 2.18-4.12).
Combined BRAF/MEK inhibition appeared associated with a lower risk for serious adverse events than BRAF alone (OR = 0.84; 95% CI, 0.66-1.06).
“Our systematic review and network meta-analysis provides the first comparison between targeted therapies and immune checkpoint inhibitors for treatment-naive, BRAF–mutated advanced melanomas,” Devji and colleagues wrote. “Though limited by a sparse network and a lack of OS data for CTLA-4/PD-1, this analysis provides an evidence-based framework to inform clinical decision-making. Our results show that OS is best with either PD-1 or combined BRAF/MEK inhibition. The favorable safety profile of PD-1 inhibitors supports using this treatment option as first-line therapy in circumstances where rapid response is not a priority.” – by Andy Polhamus
Disclosure: The researchers report no relevant financial disclosures.
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