Need PD1

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2/2/2014 12:36pm
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Replies: 3

My husband has a rapidly progressing Mucosal Melanoma with a NRAS mutaion. He was diagnosed in August with a local tumor and is already stage IV with mets in multiple organs and unable to work.  He enrolled in the Merck PD1 vs ipi trial and got randomized to ipi, his oncologist did not think ipi a good option as he is progresing so fast there is not enough time to wait and see if he is one of the lucky ones that ipi works for.  Instead we went with a combination (tram and GSK795) to block NRAS (just started on Friday),  we were really lucky to get in tthe trial, but this is an unproven theray since NRAS has been very difficult to target and I need to find a back up if he does not respond, or it the toxicity is too much.  We don't have 6 to 9 months to wait for PD1 to be approved by the FDA and it seems really difficult to find any open PD1 trials. I'd be really grateful for any leads?

Momrn5 - (2/2/2014 - 2:22pm)

Go to the thread Treatment Option Updates.  They talk about some treatments for NRAS mutation.  The thread is recent. So it should be coming up on your page.  I am new here so not much else to offer. Sorry for your trouble and Good Luck. 

JerryfromFauq - (2/3/2014 - 1:45am)

Correlation of NRAS Mutations with Clinical Response to High Dose IL-2 in Patients with Advanced Melanoma

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241890/

Abstract

The purpose of this study is to identify clinical and molecular characteristics of melanoma patients that predict response to high-dose interleukin-2 (HD IL-2) in order to improve patient selection for this approved but toxic therapy.

We reviewed the records of 208 patients with unresectable stage III/IV melanoma treated with HD IL-2 at The University of Texas M.D Anderson Cancer Center (MDACC) (n=100) and Beth Israel Deaconess Medical Center (BIDMC) (n=108) between 2003 and 2009. The BRAF and NRAS mutation status of the tumors was determined for patients with available tissue samples and the mutation status and clinical characteristics were compared to clinical outcomes. Pre-treatment serum lactate dehydrogenase (LDH) levels were available for most patients (n=194). Tissue was available for mutational analysis on a subset of patients (n=103) and the prevalence of mutations was as follows: BRAF 60%, NRAS 15%, WT/WT 25%. In the subset of patients for which mutational analysis was available, there was a significant difference in the response rate based on the mutation status: NRAS 47%, BRAF 23%, and WT/WT 12% (p=0.05). Patients with NRAS mutations had non-statistically longer overall survival (5.3 versus 2.4 years, p=0.30) and progression free survival (214 versus 70 days, p=0.13). Patients with an elevated LDH had a decreased PFS (46 versus 76 days, p<0.0001), decreased OS (0.56 versus 1.97 years, p<0.0001), and trended toward a decreased response rate (7% versus 21%, p=0.08). NRAS mutational status is a new candidate biomarkers for selecting patients with melanoma for HD IL-2 treatment.

 

I'm me, not a statistic. Praying to not be one for years yet.

kylez - (2/3/2014 - 9:58am)

Hi Elizabeth, I believe we met on Saturday. 

From looking around for myself, Portland Providence Medical Center in Oregon may have a couple of combo anti-PD1 trials opening sometime around April or so. Limited slots, "dose expansion" arms of two phase 1 trials. One is NCT01714739, one is NCT01968109.

Hope your husband gets some immediate relief on the new combo just started.

- Kyle