Wednesday, January 20, 2016

BRAFi as neoadjuvant - Now we're talk'n!!!

BRAF inhibition for advanced locoregional BRAF V600E mutant melanoma:  a potential neoadjuvant strategy.  Sloot, Zager, Kedchadkar...Weber, Sondak, Gibney.  Melanoma Res. 2/2016.

"Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can be utilized as a neoadjuvant strategy. Data on patients with advanced locoregional BRAF V600E mutant melanoma treated with BRAF-targeted therapy at Moffitt Cancer Center were analyzed to determine response rates, subsequent resection rates after tumor downsizing, pathologic responses, and patient survival. Fifteen patients with locoregional disease treated with BRAF-targeted therapy, either BRAFi alone (vemurafenib; 11 patients) or a combination of BRAFi and an MEK inhibitor (dabrafenib plus trametinib or placebo; four patients), were identified. The median age was 50 years; the median follow-up was 25.4 months. The median BRAF-targeted therapy treatment duration was 6.0 months. Response Evaluation Criteria In Solid Tumors-based evaluation demonstrated objective response in 11 patients (73.3%). Six patients underwent resection of the remaining disease after therapy. Pathological analysis showed complete pathologic response (n=2), partial pathologic response (n=2), or no pathologic response (n=2). Four of six patients undergoing surgery have been alive for more than 2 years, including three patients currently free from active disease. No complications attributable to BRAF-targeted therapy were observed in the perioperative period. Dose reduction or discontinuation because of toxicities occurred in 10/15 patients. Neoadjuvant BRAF-targeted therapy may be effective in advanced locoregional BRAF V600E mutant melanoma patients in increasing resectability, yielding pathological responses, and achieving prolonged survival."

Adjuvant treatment provides positive benefits!  Here's more adjuvant trial results:  From my NED nivo/Opdivo trial as well as one with ipi!

Here are a few amazing quotes:  

 From the Nivo trial (published Dec 2014!!!) ~ "Our data suggest that nivo is clinically active in resected stage IIIC/IV melanoma, based on low rate of relapse (10 of 33), impressive relapse-free survival - estimated RFS of 47.1 months, and median overall survival not yet reached with over 32 months of follow up."

And this from the ipi ~ "Adjuvant ipi significantly improved recurrence-free survival for patients with completely resected high-risk stage III melanoma."

What are we waiting on???  Come on researchers!  FDA?!!!  Drug companies????!!!!  Hang in there, Ratties.  You rock! - c 


  1. Celeste,
    Did these patients continue with inhibitors after surgery? Also did the article state if the 3/6 were the complete responders or the partial or non. I'm a little confused by the statement 11 people showed a objective response but then out of the six that had surgery 2 then showed no pathologic response. As you know thus is basically what i did for treatment. I was on 4.5 months not 6 and discontinued drugs 3 days before surgery.

  2. As I understand it....15 folks were treated for an average of 6 months with either BRAFi alone (11) or a BRAF/MEK combo {though some got placebo instead of MEK}(4). Of those 15...11 showed a response. The remaining....on general examination did not. Still an "objective response" is not necessarily a "complete response". So....6 patients elected to have surgery to see if the remaining "something" left after therapy at their local melanoma site was "something" or not. Of those 6: 2 had complete resolution, 2 had partial resolution, and 2 had no response at all when the samples were evaluated by patients - 11 objective responses leaves guess the 2 with no response plus the 2 with partial response. Still...4 of those 6 have been alive for more than two years. Not definitively written...but the most logical scenario given the data. Since it says they were treated for an average of 6 months with meds....I doubt these patients continued that line of treatment post study....but I don't know for sure. I'm telling you...trials and how they are reported is a tricky business!!! Hang in there! c