BRAF Negative

Another mutation notso commonly tested for is NRAS (about 20% of melanomas). Mine tested positive foe NRAS G12A. UCSF sequenced mine, maybe because they’re an academic institution. There’s at least 5 trials for NRAS patients, including one of the RAF265 trials. For the NRAS trials, go to http://www.mycancergenome.org/content/disease/melanoma/nras/85 and then click on the clinical trials tab. The common theme seems to be MEK inhibitors.

Another mutation notso commonly tested for is NRAS (about 20% of melanomas). Mine tested positive foe NRAS G12A. UCSF sequenced mine, maybe because they’re an academic institution. There’s at least 5 trials for NRAS patients, including one of the RAF265 trials. For the NRAS trials, go to http://www.mycancergenome.org/content/disease/melanoma/nras/85 and then click on the clinical trials tab. The common theme seems to be MEK inhibitors.

Another mutation notso commonly tested for is NRAS (about 20% of melanomas). Mine tested positive foe NRAS G12A. UCSF sequenced mine, maybe because they’re an academic institution. There’s at least 5 trials for NRAS patients, including one of the RAF265 trials. For the NRAS trials, go to http://www.mycancergenome.org/content/disease/melanoma/nras/85 and then click on the clinical trials tab. The common theme seems to be MEK inhibitors.

Eric, I thought you and your wife were getting expert opnions from both UCLA and MD Anderson. What did they recommend?

Also, many oncologists think that some of the most promising treatments are still in clinical trials or are about to start clinical trials. Whatever your wife takes now may possibly disqualify her from an otherwise attractive clinical trial in the future. So be sure to discuss with your oncologists who are famliar with current or soon-to-be recruiting clinical trials a multi-step treatment plan. In other words, if Yervoy fails or your wife subsequently progresses after Yervoy, what would they recommend next?

For example, I have heard on this forum that in order to qualify for an anti-PD1 trial you have to have already had Yervoy and then progressed. Is that true? And if your wife takes Yervoy would she qualify for an anti-PD-1 trial? Will any such trials still be open? 

These are difficult and complex questions to which there is probably no "correct" answer. However, it's always good to have a Plan B and a Plan C before  you start Plan A. I hope and expect that is what you gained from your consults at UCLA and MD Anderson. 

Eric, I thought you and your wife were getting expert opnions from both UCLA and MD Anderson. What did they recommend?

Also, many oncologists think that some of the most promising treatments are still in clinical trials or are about to start clinical trials. Whatever your wife takes now may possibly disqualify her from an otherwise attractive clinical trial in the future. So be sure to discuss with your oncologists who are famliar with current or soon-to-be recruiting clinical trials a multi-step treatment plan. In other words, if Yervoy fails or your wife subsequently progresses after Yervoy, what would they recommend next?

For example, I have heard on this forum that in order to qualify for an anti-PD1 trial you have to have already had Yervoy and then progressed. Is that true? And if your wife takes Yervoy would she qualify for an anti-PD-1 trial? Will any such trials still be open? 

These are difficult and complex questions to which there is probably no "correct" answer. However, it's always good to have a Plan B and a Plan C before  you start Plan A. I hope and expect that is what you gained from your consults at UCLA and MD Anderson. 

Eric, I thought you and your wife were getting expert opnions from both UCLA and MD Anderson. What did they recommend?

Also, many oncologists think that some of the most promising treatments are still in clinical trials or are about to start clinical trials. Whatever your wife takes now may possibly disqualify her from an otherwise attractive clinical trial in the future. So be sure to discuss with your oncologists who are famliar with current or soon-to-be recruiting clinical trials a multi-step treatment plan. In other words, if Yervoy fails or your wife subsequently progresses after Yervoy, what would they recommend next?

For example, I have heard on this forum that in order to qualify for an anti-PD1 trial you have to have already had Yervoy and then progressed. Is that true? And if your wife takes Yervoy would she qualify for an anti-PD-1 trial? Will any such trials still be open? 

These are difficult and complex questions to which there is probably no "correct" answer. However, it's always good to have a Plan B and a Plan C before  you start Plan A. I hope and expect that is what you gained from your consults at UCLA and MD Anderson. 

Yes, everything you are saying makes perfect sense. As usual, you seem to be a quick learner and a clear thinker. I will poke around and see if I can find anything else that might be good for a BRAF negative patient.

My only suggestion is that in the future you push your oncologists a little harder. Your UCLA oncologist seems to have presented you with 2 options for Plan A (yervoy or yervoy + anti-PD1), which is fine. But I think before your wife starts any treatment, you should discuss with your oncologist(s) Plan A AND Plan B AND Plan C. I, personally, would not accept an "let's see where things stand when we get there" answer because any treatment you get today MIGHT eliminate you from some other important treatment tomorrow. Better to think it through ahead of time and hope you never need a Plan B.  

Yes, everything you are saying makes perfect sense. As usual, you seem to be a quick learner and a clear thinker. I will poke around and see if I can find anything else that might be good for a BRAF negative patient.

My only suggestion is that in the future you push your oncologists a little harder. Your UCLA oncologist seems to have presented you with 2 options for Plan A (yervoy or yervoy + anti-PD1), which is fine. But I think before your wife starts any treatment, you should discuss with your oncologist(s) Plan A AND Plan B AND Plan C. I, personally, would not accept an "let's see where things stand when we get there" answer because any treatment you get today MIGHT eliminate you from some other important treatment tomorrow. Better to think it through ahead of time and hope you never need a Plan B.  

Yes, everything you are saying makes perfect sense. As usual, you seem to be a quick learner and a clear thinker. I will poke around and see if I can find anything else that might be good for a BRAF negative patient.

My only suggestion is that in the future you push your oncologists a little harder. Your UCLA oncologist seems to have presented you with 2 options for Plan A (yervoy or yervoy + anti-PD1), which is fine. But I think before your wife starts any treatment, you should discuss with your oncologist(s) Plan A AND Plan B AND Plan C. I, personally, would not accept an "let's see where things stand when we get there" answer because any treatment you get today MIGHT eliminate you from some other important treatment tomorrow. Better to think it through ahead of time and hope you never need a Plan B.  

there is a dose escalation trial out there that uses IL 21 and anti pd1, and another that is similar that combines IL 21 with yervoy.

I was pretty interested in the first one, but it is FULL in seattle with a long waiting list.

the number on this trial is NCT01629758, ..but I'm not sure where it's being offered outside of Seattle.

there is a dose escalation trial out there that uses IL 21 and anti pd1, and another that is similar that combines IL 21 with yervoy.

I was pretty interested in the first one, but it is FULL in seattle with a long waiting list.

the number on this trial is NCT01629758, ..but I'm not sure where it's being offered outside of Seattle.

there is a dose escalation trial out there that uses IL 21 and anti pd1, and another that is similar that combines IL 21 with yervoy.

I was pretty interested in the first one, but it is FULL in seattle with a long waiting list.

the number on this trial is NCT01629758, ..but I'm not sure where it's being offered outside of Seattle.

Wendy, Eric,

(good job remembering that article Wendy! I should have remembered too)

One thing about NRAS mutated melanoma is that NRAS and BRAF mutations are mutually exclusive if I remember correctly. So if 60% of patients have BRAF, and 20% of patients have NRAS, then if your wife doesn't have BRAF (not in that 60%) then she has a 50% chance of being in the 20% of the remaining 40% with an NRAS mutation. 

So maybe a question fo UCLA would be, can they test your wife for the NRAS mutation? UCSF did for me, before I even had heard of NRAS. They're both UCs, so…? 

So if your wife falls in that 20%, the article is saying that NRAS patients seem to respond well to immunotherapies — specifically IL-2 but perhaps more generally to other immune therapies as well: “Recent data for mutated NRAS as a predictive factor for response to high-dose interleukin 2 reinforces the notion of immunotherapies as front-line treatment for NRAS-mutated metastatic melanoma,” … With the caveat that Catherine Poole mentions there is not a wide enough set of data yet to fully confirm these findings. 

And while MEK inhibitors are mentioned for NRAS as well, they're saying at the current time they wouln't recommend it as the first therapy, but rather, immune as first therapy.

So if your wife has NRAS  mutation, is that a plan A (immune therapy) and plan B (another immune therapy or MEK inhibitor) and maybe plan C? (maybe there'll be combined trials of immune and MEK for NRAS patients sometime in the future?)

Wendy, Eric,

(good job remembering that article Wendy! I should have remembered too)

One thing about NRAS mutated melanoma is that NRAS and BRAF mutations are mutually exclusive if I remember correctly. So if 60% of patients have BRAF, and 20% of patients have NRAS, then if your wife doesn't have BRAF (not in that 60%) then she has a 50% chance of being in the 20% of the remaining 40% with an NRAS mutation. 

So maybe a question fo UCLA would be, can they test your wife for the NRAS mutation? UCSF did for me, before I even had heard of NRAS. They're both UCs, so…? 

So if your wife falls in that 20%, the article is saying that NRAS patients seem to respond well to immunotherapies — specifically IL-2 but perhaps more generally to other immune therapies as well: “Recent data for mutated NRAS as a predictive factor for response to high-dose interleukin 2 reinforces the notion of immunotherapies as front-line treatment for NRAS-mutated metastatic melanoma,” … With the caveat that Catherine Poole mentions there is not a wide enough set of data yet to fully confirm these findings. 

And while MEK inhibitors are mentioned for NRAS as well, they're saying at the current time they wouln't recommend it as the first therapy, but rather, immune as first therapy.

So if your wife has NRAS  mutation, is that a plan A (immune therapy) and plan B (another immune therapy or MEK inhibitor) and maybe plan C? (maybe there'll be combined trials of immune and MEK for NRAS patients sometime in the future?)

Wendy, Eric,

(good job remembering that article Wendy! I should have remembered too)

One thing about NRAS mutated melanoma is that NRAS and BRAF mutations are mutually exclusive if I remember correctly. So if 60% of patients have BRAF, and 20% of patients have NRAS, then if your wife doesn't have BRAF (not in that 60%) then she has a 50% chance of being in the 20% of the remaining 40% with an NRAS mutation. 

So maybe a question fo UCLA would be, can they test your wife for the NRAS mutation? UCSF did for me, before I even had heard of NRAS. They're both UCs, so…? 

So if your wife falls in that 20%, the article is saying that NRAS patients seem to respond well to immunotherapies — specifically IL-2 but perhaps more generally to other immune therapies as well: “Recent data for mutated NRAS as a predictive factor for response to high-dose interleukin 2 reinforces the notion of immunotherapies as front-line treatment for NRAS-mutated metastatic melanoma,” … With the caveat that Catherine Poole mentions there is not a wide enough set of data yet to fully confirm these findings. 

And while MEK inhibitors are mentioned for NRAS as well, they're saying at the current time they wouln't recommend it as the first therapy, but rather, immune as first therapy.

So if your wife has NRAS  mutation, is that a plan A (immune therapy) and plan B (another immune therapy or MEK inhibitor) and maybe plan C? (maybe there'll be combined trials of immune and MEK for NRAS patients sometime in the future?)

The head of the UCSF dermatology clinic has told me (before these articles recently came out) that they're looking for targeted therapies for their NRAS patients (of which I'm one), but as of a few months ago nothing has really been panning out — other than immune therapies which are not targeted to particluar mutations. 

So for your wife, they're doing more sequencing besides BRAF V600E? Maybe that meas they're looking for some other possible mutations — which could be NRAS (about 20% patients) and/or C-KIT (about 10% cutaneous/skin melanoma patients, and 10-40% of acral and mucosal melanoma patients). Your wife may or may not have the NRAS mutation, and may or may not have the C-KIT mutation.  

What I was trying to say before is that with the caveat of a big MAYBE so far, a couple of recently published articles are saying that for NRAS mutated patients (1/2 of the remaining 40% or so BRAF negative patients), the immune therapy IL-2, as well as possibly other immune therapies (Yervoy, anti-PD1, IL-21 and so forth) there may be a stronger response. And therefore immune therapies should be considered as the first-line therapy for NRAS patients — but larger studies are needed to confirm.

Also with the caveat of a big MAYBE, there are some indications that targeted thereapies for inhibiting MEK may work in NRAS patients, but on average not yet as well as immune therapies.

Hope that helps. Very interesting that they're doing more mutation testing.

– Kyle

The head of the UCSF dermatology clinic has told me (before these articles recently came out) that they're looking for targeted therapies for their NRAS patients (of which I'm one), but as of a few months ago nothing has really been panning out — other than immune therapies which are not targeted to particluar mutations. 

So for your wife, they're doing more sequencing besides BRAF V600E? Maybe that meas they're looking for some other possible mutations — which could be NRAS (about 20% patients) and/or C-KIT (about 10% cutaneous/skin melanoma patients, and 10-40% of acral and mucosal melanoma patients). Your wife may or may not have the NRAS mutation, and may or may not have the C-KIT mutation.  

What I was trying to say before is that with the caveat of a big MAYBE so far, a couple of recently published articles are saying that for NRAS mutated patients (1/2 of the remaining 40% or so BRAF negative patients), the immune therapy IL-2, as well as possibly other immune therapies (Yervoy, anti-PD1, IL-21 and so forth) there may be a stronger response. And therefore immune therapies should be considered as the first-line therapy for NRAS patients — but larger studies are needed to confirm.

Also with the caveat of a big MAYBE, there are some indications that targeted thereapies for inhibiting MEK may work in NRAS patients, but on average not yet as well as immune therapies.

Hope that helps. Very interesting that they're doing more mutation testing.

– Kyle

The head of the UCSF dermatology clinic has told me (before these articles recently came out) that they're looking for targeted therapies for their NRAS patients (of which I'm one), but as of a few months ago nothing has really been panning out — other than immune therapies which are not targeted to particluar mutations. 

So for your wife, they're doing more sequencing besides BRAF V600E? Maybe that meas they're looking for some other possible mutations — which could be NRAS (about 20% patients) and/or C-KIT (about 10% cutaneous/skin melanoma patients, and 10-40% of acral and mucosal melanoma patients). Your wife may or may not have the NRAS mutation, and may or may not have the C-KIT mutation.  

What I was trying to say before is that with the caveat of a big MAYBE so far, a couple of recently published articles are saying that for NRAS mutated patients (1/2 of the remaining 40% or so BRAF negative patients), the immune therapy IL-2, as well as possibly other immune therapies (Yervoy, anti-PD1, IL-21 and so forth) there may be a stronger response. And therefore immune therapies should be considered as the first-line therapy for NRAS patients — but larger studies are needed to confirm.

Also with the caveat of a big MAYBE, there are some indications that targeted thereapies for inhibiting MEK may work in NRAS patients, but on average not yet as well as immune therapies.

Hope that helps. Very interesting that they're doing more mutation testing.

– Kyle

In the summer of 2011 I didn't qualify for the anti-PD1 trial (which was my first choice) and my only option was Yervoy. But I've had stable or shrinking disease since that summer, after Yervoy (and SRS and craniotomy). So even though it's not anti-PD1, it seems like Yervoy probably did something for me, and it's done something for quite a few other folks too. At the time I kind of dismissed Yervoy because it wasn't anti-PD1, but it seems to have helped me stay stable/shrinking for all this time. So… I don't think I shot myself in the foot with Yervoy. My only other previous treatment was IL-2. 

In the summer of 2011 I didn't qualify for the anti-PD1 trial (which was my first choice) and my only option was Yervoy. But I've had stable or shrinking disease since that summer, after Yervoy (and SRS and craniotomy). So even though it's not anti-PD1, it seems like Yervoy probably did something for me, and it's done something for quite a few other folks too. At the time I kind of dismissed Yervoy because it wasn't anti-PD1, but it seems to have helped me stay stable/shrinking for all this time. So… I don't think I shot myself in the foot with Yervoy. My only other previous treatment was IL-2. 

In the summer of 2011 I didn't qualify for the anti-PD1 trial (which was my first choice) and my only option was Yervoy. But I've had stable or shrinking disease since that summer, after Yervoy (and SRS and craniotomy). So even though it's not anti-PD1, it seems like Yervoy probably did something for me, and it's done something for quite a few other folks too. At the time I kind of dismissed Yervoy because it wasn't anti-PD1, but it seems to have helped me stay stable/shrinking for all this time. So… I don't think I shot myself in the foot with Yervoy. My only other previous treatment was IL-2. 

Did I shoot myself in the foot by going with Ipilimumab ????

I would say no as my husband has been on Ipi (Yervoy) for 2 years now and if this would start to fail then his oncologist is saying Anti PD1 would be the next avenue.

Hope this helps ease your mind.

Judy (loving wife of Gene)

Did I shoot myself in the foot by going with Ipilimumab ????

I would say no as my husband has been on Ipi (Yervoy) for 2 years now and if this would start to fail then his oncologist is saying Anti PD1 would be the next avenue.

Hope this helps ease your mind.

Judy (loving wife of Gene)

Did I shoot myself in the foot by going with Ipilimumab ????

I would say no as my husband has been on Ipi (Yervoy) for 2 years now and if this would start to fail then his oncologist is saying Anti PD1 would be the next avenue.

Hope this helps ease your mind.

Judy (loving wife of Gene)

The ones my samples tested positive for are NRAS G12A and BRAF G466E.

The ones my samples tested positive for are NRAS G12A and BRAF G466E.

The ones my samples tested positive for are NRAS G12A and BRAF G466E.