Saturday, May 28, 2016

ASCO 2016 - Anti-PD1 for acral and mucosal melanoma

Acral and mucosal melanoma often fail to play by even the random rules that other melanoma tumors share and as such make treatment of them even more difficult.  But...there is this:

Clinical activity of anti-programmed death-1 (PD-1) agents in acral and mucosal melanoma.  ASCO 2016. #9516.  J Clin Oncol 2016.  Munhoz, Shoushtari, Kuk, et al.

Background: Antibodies against PD-1 resulted in a paradigm shift in the management of melanoma. Nevertheless, melanoma is a heterogeneous disease: compared to cutaneous melanoma, mucosal melanoma (MM) and acral melanoma (AM) have distinct genetic and clinical characteristics, lower somatic mutational burden, and poorer prognosis. We sought to investigate the efficacy of PD-1 blockade in patients (pts) with advanced mm and AM. Methods: We conducted a multicenter retrospective study of pts with advanced mm or AM treated with nivolumab or pembrolizumab. Clinical, pathologic, and treatment data were retrieved from electronic medical records. Response rates were assessed by RECIST v1.1 and survival intervals were calculated using the Kaplan-Meier method. Variables associated with response and survival were investigated. Results: Sixty pts were identified; 35 (58%) with mm and 25 (42%) with AM. Fifty-one (85%) pts had received prior therapy, including 77% with prior ipilimumab. Forty pts (67%) received pembrolizumab at 2mg/kg or 10mg/kg and 20 (33%) received nivolumab at 1mg/kg or 3mg/kg every 2-3 weeks. Objective response rate (ORR)  was 23% (10-40%) in mm and 32% (15-54%) in AM. ORR did not vary by age, primary site, or prior therapy outcomes. With a median follow-up of 10.6 months (mo) for mm and 20 mo for AM, the median progression-free survival was 3.9 mo and 4.1 mo, respectively. Median overall survival for the entire cohort was 16.8 mo; in mm it was 12.4 mo, and in AM 31.7 mo. Only two pts (3%) discontinued treatment due to toxicity. Conclusions: PD-1 blockade resulted in clinically meaningful activity in pts with mm and AM. Response rates and safety profile were comparable to published clinical trials which largely consisted of cutaneous melanoma and support the use of PD-1 blockade for mm and AM as well. The role of specific driver mutations, immunologic infiltrates and potential biomarkers of response and resistance in these melanoma subtypes needs further investigation.

Here, the roughly 40% response rates with anti-PD1 for treatment naive cutaneous melanoma patients were not achieved.  But, 85% of these patients had been previously treated....something many studies shows diminishes response rate and then there is the fact we are dealing with mucosal and acral melanoma.  Response rates of 23 and 32% are certainly something and definitely worth pursuing!!!  Interestingly, mucosal melanoma can often be NRAS positive.  Earlier I posted this: Good news for NRAS positive folks re: Anti-PD1 In that report, where NRAS positive patients were evaluated for response to IL2, ipi, vs anti-PD1 they found:  

"Within specific immune therapy types, patients with NRAS-mutant melanoma experienced the greatest benefit in CR/PR compared to patients with WT melanoma when treated with anti-PD1/PD-L1 agents (70% vs 20%)."   
Which got me thinking:  "A ray of light for folks with NRAS mutation. And maybe one more reason not to make them go through ipi before they get to take anti-PD1???!!!!!"  
Not all mucosal or acral melanoma are NRAS positive...but that info would probably be a good thing to find out!  Hang in there, dear ones!  Hang in there.   - c


  1. I was diagnosed with MM in October - Tumor removed in November - My results show I am NRAS positive. I am scheduled to begin 6-7 weeks of radiation therapy in Boston with the proton radiation machine. I have been to two oncologists and they both say they truly don't have enough data (good hospitals in Boston). This is the first I have heard of NRAS positive. Can you please tell me more about this. Is this treatment most effective after radiation? How and where it is administered.

    Thank you,

  2. by MM I mean mucosal melanoma also called sinonasal melanoma

  3. Anti-PD 1 is immunotherapy that stimulates your immune system to kill your melanoma. In cutaneous melanoma response rates are about 40%. Clearly, MM does not respond as well...but this report contends that those patients CAN respond. Anti-PD1 is administered IV. There are two almost equal products- nivolumab (Opdivo) and pembrolizumab (Keytruda). For all melanoma patients, immunotherapy has been found to work better when combined with radiation. If you put 'radiation and immunotherapy' in the search bubble at the top left of this blog, you will find many articles related to that.

    I am concerned that you are seeing docs that don't know about anti-PD1. If that is what you are stating, then you need to find new melanoma specialist asap!

    On the other hand....if you are talking about still need a melanoma specialist...even more so....not just a general oncologist. As big a bear as melanoma is....NRAS is even more difficult to treat. Depsite this article, it is controversial to treat NRAS mutant mel with anti-PD1, because I have reports that say it can work and others that say the results are minimal. Again...put 'NRAS' in the search bubble. There are studies that note aspirin can be helpful as well as MEK inhibitors. These are things that a melanoma specialist should be able to discuss with that you can make the best choice and treatment plan for you. I wish you well.