Deeper inhibition of the mitogen-activated protein kinase (MAPK) pathway by targeting both MEK and BRAF may help improve progression-free survival (PFS) outcomes in patients with advanced BRAF V600–mutated melanoma, according to a retrospective analysis.
“Therapeutic targeting of the constitutively active MAPK signaling pathway in patients with advanced melanomas harboring the BRAF V600 mutation has demonstrated meaningful clinical benefit,” wrote study authors led by Matthew J. Wongchenko, of Genentech in San Francisco. “However, tumor recurrence 6 to 7 months after initiation of treatment with BRAF inhibitor monotherapy is common.”
The investigators conducted a retrospective analysis of patients in the phase III coBRIM trial, to determine the effects of BRAF V600 allelic balance, coexisting mutations, loss of PTEN expression, and other factors on PFS. The trial compared the combination of the MEK inhibitor cobimetinib and the BRAF inhibitor vemurafenib vs vemurafenib monotherapy; both of these medications are marketed by Genentech. Results of the analysis were published in JCO Precision Oncology.
Of 495 total patients, frequencies of BRAF V600 mutant alleles were available in 400. Variant allele frequency ranged from 5% to 90%, with a median of 33.9%, and it did not appear to have any correlation with PFS. The hazard ratios (HR) for those with frequency above and below the median were 0.97 and 1.11, respectively.
Source: Cancer Network
