Some Treatment option updates

Posted By
2/1/2014 1:30pm
Replies: 3

I am at a patient and physician meeting the MRF is hosting and hearing data from some excellent melanoma doctors.  A couple of things have stood out so far:

We have seen data that for patients whose tumor has the BRAF mutation, combinging a BRAF inhibitor plus a MEK inhibitor is better than the BRAF inhibitor alone.  We also know that most patients respond to these drugs for a few months then the tumor finds away to work around these inhibitors.  The question remains whether you should take a BRAF inhibitor first and save the combination for after the BRAF alone stops working.  Data now shows that people who have progressed on BRAF monotherapy do not perform as well on the combination as do people who have not had prior BRAF therapy.  This suggests it is better to start with the combination.

About 50% of melanomas have the BRAF mutation.  Another 20% have an NRAS mutation.  Data now suggests that patients with an NRAS mutation respond better to the immunotherapy drug ipilimumab (Yervoy).  This may be because NRAS patients tend to be older and more tied to long-term UV exposure, and older patients tend to have more mutations in their tumors overall.  This, in turn, may make those tumors easier targets for the immune system once it becomes activiated against tumor cells.



POW - (2/1/2014 - 2:08pm)

Hi, Tim-

I love the way you provide us with "hot off the presses" from the scientific conferences you attend. Thank you very much and keep 'em coming!

The link between NRAS and ipi is new to me. Who are the author(s) of that presentation? I would like to be able to follow their work in the future.

Tim, Did you see this NIH aricle that I discussed with Dr Atkins at the MRF symposium in Georgetown?


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

The publisher's final edited version of this article is available at J Immunother
See other articles in PMC that cite the published article.


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.


We're stepping closer to learning what for who!


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

I attended this meeting (Tim, I sat next to you in the morning). It was very informative, and timely for me. Here are my notes (may or may not be accurate) from Dr. Weber's talk:

Mutations: There are currently 3 mutations commonly tested for. In a year there will be 30 tested for.

DTIC: Dr. Weber has not given this in years.

(Echoing Tim above) Dr. Weber would never prescribe BRAF alone today. Right from the start he would prescribe the BRAF+MEK combo. That's also what he would do if he were a patient.

There is still no proven marker for immune therapies. He has been working on trying to find one for 5 years.

TVEC -- he is seeing good results from this. With TVEC they inject a tumor with a virus that expresses GM-CSF (aka TVEC). The comparator is straight GM-CSF, which he says has not seemed particularly efficacious on its own.

Trial participants should always shoot for combo therapies if possible. That's what he would do if he were a patient.

Tim -- thank you for putting this event on.

- Kyle