Those of us who have lived in melanoma world prior to 2011, KNOW the extreme desperation that a melanoma diagnosis gave us given that there were NO particularly viable treatments. Folks were relegated to decarbazine (also called DTIC, doesn't work!!), interferon (DOESN'T work!!!) or IL2 (works a little with a ??? 10% response rate). So, as the BRAF inhibitors, especially when we learned to combine them with MEK inhibitors, and immunotherapy (ipi, nivo, pembro and the ipi/nivo combo) became available with response rates unlike anything we had ever had....it was nothing short of a miracle! Then, over the years...reality set in.
BRAF/MEK combo's can attain response rates of up to 70% in some studies, but responses are notoriously limited when tumors learn ways to work around that control in about 9-12 months depending on the study. There are, however, those who are well maintained on these drugs for 3-5 years...but they are not the norm. Then, we have to face the fact that to attain any response at all to these meds one must have BRAFV600 mutated melanoma...which leaves out about half of us! Here is one of my latest BRAFi posts addressing a combo that may make those response rates a little more extended: Encorafenib/binimetinib, a BRAF/MEK combo = 14.9 month PFS
Here is a link to a nice review of BRAF/MEK targeted therapy by Eroglu and Ribas: Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy
Immunotherapy has proven to have much more durable responses though with decreased response rates. For about 15% of folks who take ipi, 40% of us who take nivo or pembro, and 50%+ of those who take the ipi/nivo combo - a response of some degree will be attained. But, once again, about half of melanoma patients will NOT respond AND when reports talk about a response (ORR - overall response rate)....they are not talking about a group of "complete responses" (CR). They are talking about a group that INCLUDES CR, PR (partial response), and SD (stable disease). As yesterday's post (ASCO 2017: Outcomes after stopping immunotherapy in melanoma) made clear...durability of these responses are better than with any other treatments we have. But, we still don't find folks readily using the word "cure", now do we???
So, what does all that mean? It means, "We've come a long way, Baby!!!" BUT....we've got a long way to go! We've got folks who never gain response to treatment. We've got folks who respond, then progress and need further treatment. I had hoped that this year's ASCO would present the next great melanoma treatment! I had hoped that one of the "novel therapies" or new "combo's" would have numbers that would ensure new treatments that are effective and readily available to melanoma patients in need. Sadly, that has not really been the case. I found nothing substantial about IDO inhibitors, for instance. However, I am going to hold out hope for that treatment as well as others...as maturation of data takes far longer than we would like it to. Over the next few days I will be presenting the abstracts that DO address novel therapies and combo's.......
Today's abstract looks at pembro combined with entinostat (an histone deacetylase inhibitor or 'HDAC'). Here is what I have on HDAC in general from late 2016: HDAC (Histone deacetylase) inhibitors for melanoma...and....The Future for Melanoma Treatment = Combo's! Dr. Weber breaks it down - The first article linked gives a nice explanation of what HDAC inhibitors are hoped to do. Namely, "Existing evidence supports the hypothesis that HDAC inhibitors (HDACi) may sensitize melanoma cells to immunotherapy and targeted therapy and hence bear therapeutic potential concurrent with immune checkpoint blockade or BRAF and MEK inhibition." Here's the abstract:
As I best understand it: There were 4 responses in 13 melanoma patients. There were 4 with stable disease. PD-L1 expression in these patients were: 31% = negative, 46% = positive, and 23% were not evaluable. All patients had progressed on or after: pembro (54%), nivo (46%), ipi (62%), BRAFi (15%). Three additional arms are being added: 1. patients with NSCLC with no prior anti-PD-1 tx, 2. pts with NSCLC who progressed on anti-PD-1, 3. colorectal patients with no prior anti-PD-1.
Just so you all know...B and Eric provide invaluable help to me in researching treatment options for dear ones who progress on existing treatments. Most recently in seeking trials that might be effective and for which dear Josh and Paul and so many others may qualify. And those "exclusions" are extremely problematic!!! You can't have had this. You can't have had that. You must be "x number" of days post this or that. This is NOT okay! Folks with progressive disease do not have time for a "washout" period. Folks with progressive disease need TREATMENT, not exclusions!! One more time....."You can put folks who have had multiple treatments in their own arm, Big Pharma CEO Person!!!!!!"
For what it's worth. More abstracts of novel therapies and combo's will be coming in the next few days with less preamble. However, as much as I push for those in need of care....I will forever push in honor of those who fought even harder than the rest of us. This one's for Joshie. - c