Melanoma is a complicated disease entity to say the least. Tumors, that are now all lumped together as 'melanoma' demonstrate many different mutations and develop via a variety of pathways. About half of us are BRAF positive. Aboust 20% of us have the NRAS mutation. Then there's all sorts of other delineations! This post: What tangled paths we weave...
Which contains this diagram:
|Probably makes the pathway as clear as anything else!!|
Thus far, targeted therapy (using a combination of a BRAF inhibitor with a MEK inhibitor) has been found to be most effective for only those with a V600 BRAF mutated melanoma. However, this post in 2016 addresses how nelfinavir (also called Viracept, an HIV protease ihibitor) can be used to decrease resistance to those meds in both BRAF and NRAS mutant melaonma: Stopping resistance to targeted therapy- nelfinavir- for BRAF and NRAS mutant melanoma
Here an older cardiac drug was paired with a MEK inhibitor: Digoxin and trametinib for BRAF wild type melanoma
Recently I posted this study in which binimetinib (a MEK inhibitor) was paired with encorafenib (a BRAF inhibitor): Encorafenib/binimetinib, a BRAF/MEK combo = 14.9 month PFS
Within it was noted that, "In March, Array withdrew its FDA new drug application for single-agent binimetinib as a treatment for patients with NRAS-mutant advanced melanoma, based on feedback from the FDA during a preplanned review meeting."
However, from ASCO 2017...this study pairs binimetinib with ribociclib (also named Kisquali [What the f@%K?????] a CDK 4/6 inhibitor, approved this year for use in HR+/HER 2 breast cancer):
So both are oral meds...given in a 28-day cycle as noted above, to 16 patients - 44% of whom had increased LDH, 44% had been previously given ipi, 31% had been previously treated with anti-PD-1 or anti-PD-L1. Meds were given for an average of 4 months. There was a confirmed partial response in 4 patients, stable disease in 7, disease progression in 3 and 2 were not evaluated. For what it's worth...
When looking at immunotherapy in NRAS patients, I posted this in 2015: Good news for NRAS positive folks, especially in regard to anti-PD1!!!! Now there is this:
In this study, 224 NRAS mutated melanoma patients were studied. 180 were treated with ipi, 98 with anti-PD-1 and 1 was given the ipi/nivo combo. The overall response rate was 15% for those treated with ipi and 34% for those treated with anti-Pd-1....which is in keeping with response rates for those drugs generally.
Good to know. - c