› Forums › General Melanoma Community › Stage 4 treatment naive – best sequencing of treatment?
- This topic has 18 replies, 5 voices, and was last updated 9 years, 10 months ago by
Jubes.
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- July 1, 2015 at 7:02 am
Hi all,
I posted about a week ago regarding my Dad who was recently diagnosed with Stage 4 melanoma in his brain (3-7 mets) and lungs (one tumor). He started whole brain radiation right away and will finish up the 10-day course of that tomorrow. The doctors are hoping that this intensive radiation will shrink some of the brain tumors so that we can try gamma knife/SRS on the brain mets later (if they have decreased in size/number). In any case, we are close to getting the BRAF test results and so I want to make sure that we know our next set of treatment options now that his radiation is almost done. We did have one visit with Dr. Thompson at SCCA but, without BRAF, we weren't able to settle on a course/sequence of treatment. And, after reading a number of posts in recent days, I want to ensure that we sequence the treatment as well as we can (especially given that his recent radiation round may help with efficacy of some of the drugs, some of these treatments need to be administered in particular orders per Medicare, some may have different efficacy given his "treatment naive" nature, etc.). From what I understand, here are our options:
1) If BRAF +, he should try to get on the Dabrafenib (Tafinlar) plus Trametinib (Mekinist) combo – which he can start right away. Also, in order to prolong resistance from developing, he can take it episodically, correct? Are there any other drugs or methods to hold off resistance? Would you recommend starting with these drugs over ipi/the anti-PD-1 options or delay these to be used as a last resort? From what I understand (and please correct me), these drugs show results faster than the ipi/anti-PD-1 options, he can continue to take steriods while on them (since he has a bit of swelling in his brain now), etc. – so those are some of the positives.
2) If BRAF -, he would have to try ipi first and have it fail before insurance (Medicare) would allow him to try Nivo or Keytruda. Or, is there a way to get Nivo or Keytruda as a first line option (similar to what was just approved in the EU)? Are any of the anti-PD-1 drugs more effective for brain mets? Or, rather than going for single drug therapy, would it be better to try to get him right into a clinical trial for the ipi/nivo combo if he is BRAF- (given its higher efficacy but yet also worse side effects)?
What else are we missing? We should hear about BRAF in a few days and so want to best understand our options and the pros/cons of sequencing – in order to be informed of whatever treatment comes recommended next. What else do we need to be asking the doctors before we figure our treatment plan? What other factors should we be considering? For example, the doctors never told us that this whole brain radiation is a one-time deal in his lifetime – that would have been helpful to know upfront. Had to make the call on that over only a few hours – very tough…
Any advice and thoughts would be appreciated! So helpful to have found this community…
Carrie
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- July 1, 2015 at 6:03 pm
Carrie,
You have basically got it straight and in a short amount of time!!! The big question for everyone in melanoma land…now that we are lucky enough to have multiple treatment options….is what treatment should I use first? What treatment should I save for later? Truth? We don't know. Different patients look at it different ways. Different docs do as well. But, we don't know. Yes, BRAFi tend to work quicker, though less long. Sometimes they are used to quickly diminish tumor burden in order to prep for surgery or to then quickly switch to immunotherapies which are known to work best when the patient has the least tumor burden. But, some folks are maintained on them for a long time. Some folks even acquire complete remission. Here is a post on that topic that I just put up: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/07/brafi-what-predicts-resistance.html
You can take prednisone while on immunotherapies if necessary. That is how side effects are treated, sometimes with a break in treatment, and then resumption…though it is not preferred. Generally, immunotherapies act more slowly…sometimes tumors even seem to "grow" on scans before responding. However, some folks respond to immunotherapies (ipi and the anti-PD1 products) rapidly.
You are correct in understanding that FDA approval of both anti-PD1 products require progression on ipi as well as BRAFi (if BRAF positive). Insurance payors usually follow those quidelines. There are those who report folks have been approved otherwise, but I have not personally seen documentation. And yes, Nivo is already approved as a first line therapy in the EU. There are MANY, MANY trials still reruiting that allow a patient to take Nivo/Opdivo or Pembro/Keytruda with various other things, like radiation for example, that allows an anti-PD1 treatment as a first step. Of course there is the nivo/ipi combo…most effective thing going…but with increased risk of side effects, as you noted.
All of these drugs have been shown in multiple studies to work in the brain. There is an ongoing study looking at Pembro in patients with brain mets. All have been found so far…to have approximately the same response rate in the brain as they do in the body. Additionally, many studies are confirming a synergistic effect between all these drugs and radiation. So, hopefully, that will work in your father's favor as well.
You are doing well by your father. Hope this helps. Celeste
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- July 3, 2015 at 8:46 am
Thank you, Celeste! We just learned this afternoon that my Dad is BRAF negative so that will narrow down our options. Does it then make sense to have him tested for NRAS (since it tends to be mutually exclusive with BRAF)? Back to learning more about all of our immunotherapy options! Really hoping something works!!!
Thank you again,
Carrie
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- July 3, 2015 at 1:08 pm
It certainly couldn't hurt to find out your dad's NRAS status. I figure the more you know about your condition the better you can think about the best treatment option. Here is some NRAS info should you need it…
This bit is new: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/01/good-news-for-nras-positive-folks.html
This is older, but with a little background: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/01/better-news-for-mek-and-brafmek-combos.html
Wishing you and your dad well. C
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- July 3, 2015 at 11:19 pm
Hi there (to both of you!),
Carrie, your father's experience sounds very similar to my fiance's. He also had several brain mets (treated with SRS, not WBR), and a tumor on the lower right lobe of his lung. He also has a tumor on his right adrenal and in his mediastinum. Dave (the fiance!), is also BRAF negative, but IS NRAS positive. I agree with Celeste, it really doesn't hurt to get tested for the NRAS mutation. It could help down the road with future treatments and/or clinical trials. There have also been some studies that could show a correlation between increased response rates and the NRAS mutation. Any and all little rays of hope help!
I think the main reason I wanted to reach out is that you mentioned that you are discussing an anti-PD1 as a first-line treatment. Although as Celeste mentioned, it is unusual, but does and can happen! Dave just received his first treatment of Keytruda (Pembro) on July 1 without any prior treatment…of course, it does depend on your insurance, but it is a possibility (FYI, Dave has Kaiser).
Wishing you and your father the best!
Katie
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- July 3, 2015 at 11:19 pm
Hi there (to both of you!),
Carrie, your father's experience sounds very similar to my fiance's. He also had several brain mets (treated with SRS, not WBR), and a tumor on the lower right lobe of his lung. He also has a tumor on his right adrenal and in his mediastinum. Dave (the fiance!), is also BRAF negative, but IS NRAS positive. I agree with Celeste, it really doesn't hurt to get tested for the NRAS mutation. It could help down the road with future treatments and/or clinical trials. There have also been some studies that could show a correlation between increased response rates and the NRAS mutation. Any and all little rays of hope help!
I think the main reason I wanted to reach out is that you mentioned that you are discussing an anti-PD1 as a first-line treatment. Although as Celeste mentioned, it is unusual, but does and can happen! Dave just received his first treatment of Keytruda (Pembro) on July 1 without any prior treatment…of course, it does depend on your insurance, but it is a possibility (FYI, Dave has Kaiser).
Wishing you and your father the best!
Katie
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- July 3, 2015 at 11:19 pm
Hi there (to both of you!),
Carrie, your father's experience sounds very similar to my fiance's. He also had several brain mets (treated with SRS, not WBR), and a tumor on the lower right lobe of his lung. He also has a tumor on his right adrenal and in his mediastinum. Dave (the fiance!), is also BRAF negative, but IS NRAS positive. I agree with Celeste, it really doesn't hurt to get tested for the NRAS mutation. It could help down the road with future treatments and/or clinical trials. There have also been some studies that could show a correlation between increased response rates and the NRAS mutation. Any and all little rays of hope help!
I think the main reason I wanted to reach out is that you mentioned that you are discussing an anti-PD1 as a first-line treatment. Although as Celeste mentioned, it is unusual, but does and can happen! Dave just received his first treatment of Keytruda (Pembro) on July 1 without any prior treatment…of course, it does depend on your insurance, but it is a possibility (FYI, Dave has Kaiser).
Wishing you and your father the best!
Katie
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- July 3, 2015 at 1:08 pm
It certainly couldn't hurt to find out your dad's NRAS status. I figure the more you know about your condition the better you can think about the best treatment option. Here is some NRAS info should you need it…
This bit is new: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/01/good-news-for-nras-positive-folks.html
This is older, but with a little background: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/01/better-news-for-mek-and-brafmek-combos.html
Wishing you and your dad well. C
-
- July 3, 2015 at 1:08 pm
It certainly couldn't hurt to find out your dad's NRAS status. I figure the more you know about your condition the better you can think about the best treatment option. Here is some NRAS info should you need it…
This bit is new: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/01/good-news-for-nras-positive-folks.html
This is older, but with a little background: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/01/better-news-for-mek-and-brafmek-combos.html
Wishing you and your dad well. C
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- July 3, 2015 at 8:46 am
Thank you, Celeste! We just learned this afternoon that my Dad is BRAF negative so that will narrow down our options. Does it then make sense to have him tested for NRAS (since it tends to be mutually exclusive with BRAF)? Back to learning more about all of our immunotherapy options! Really hoping something works!!!
Thank you again,
Carrie
-
- July 3, 2015 at 8:46 am
Thank you, Celeste! We just learned this afternoon that my Dad is BRAF negative so that will narrow down our options. Does it then make sense to have him tested for NRAS (since it tends to be mutually exclusive with BRAF)? Back to learning more about all of our immunotherapy options! Really hoping something works!!!
Thank you again,
Carrie
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- July 1, 2015 at 6:03 pm
Carrie,
You have basically got it straight and in a short amount of time!!! The big question for everyone in melanoma land…now that we are lucky enough to have multiple treatment options….is what treatment should I use first? What treatment should I save for later? Truth? We don't know. Different patients look at it different ways. Different docs do as well. But, we don't know. Yes, BRAFi tend to work quicker, though less long. Sometimes they are used to quickly diminish tumor burden in order to prep for surgery or to then quickly switch to immunotherapies which are known to work best when the patient has the least tumor burden. But, some folks are maintained on them for a long time. Some folks even acquire complete remission. Here is a post on that topic that I just put up: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/07/brafi-what-predicts-resistance.html
You can take prednisone while on immunotherapies if necessary. That is how side effects are treated, sometimes with a break in treatment, and then resumption…though it is not preferred. Generally, immunotherapies act more slowly…sometimes tumors even seem to "grow" on scans before responding. However, some folks respond to immunotherapies (ipi and the anti-PD1 products) rapidly.
You are correct in understanding that FDA approval of both anti-PD1 products require progression on ipi as well as BRAFi (if BRAF positive). Insurance payors usually follow those quidelines. There are those who report folks have been approved otherwise, but I have not personally seen documentation. And yes, Nivo is already approved as a first line therapy in the EU. There are MANY, MANY trials still reruiting that allow a patient to take Nivo/Opdivo or Pembro/Keytruda with various other things, like radiation for example, that allows an anti-PD1 treatment as a first step. Of course there is the nivo/ipi combo…most effective thing going…but with increased risk of side effects, as you noted.
All of these drugs have been shown in multiple studies to work in the brain. There is an ongoing study looking at Pembro in patients with brain mets. All have been found so far…to have approximately the same response rate in the brain as they do in the body. Additionally, many studies are confirming a synergistic effect between all these drugs and radiation. So, hopefully, that will work in your father's favor as well.
You are doing well by your father. Hope this helps. Celeste
-
- July 1, 2015 at 6:03 pm
Carrie,
You have basically got it straight and in a short amount of time!!! The big question for everyone in melanoma land…now that we are lucky enough to have multiple treatment options….is what treatment should I use first? What treatment should I save for later? Truth? We don't know. Different patients look at it different ways. Different docs do as well. But, we don't know. Yes, BRAFi tend to work quicker, though less long. Sometimes they are used to quickly diminish tumor burden in order to prep for surgery or to then quickly switch to immunotherapies which are known to work best when the patient has the least tumor burden. But, some folks are maintained on them for a long time. Some folks even acquire complete remission. Here is a post on that topic that I just put up: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/07/brafi-what-predicts-resistance.html
You can take prednisone while on immunotherapies if necessary. That is how side effects are treated, sometimes with a break in treatment, and then resumption…though it is not preferred. Generally, immunotherapies act more slowly…sometimes tumors even seem to "grow" on scans before responding. However, some folks respond to immunotherapies (ipi and the anti-PD1 products) rapidly.
You are correct in understanding that FDA approval of both anti-PD1 products require progression on ipi as well as BRAFi (if BRAF positive). Insurance payors usually follow those quidelines. There are those who report folks have been approved otherwise, but I have not personally seen documentation. And yes, Nivo is already approved as a first line therapy in the EU. There are MANY, MANY trials still reruiting that allow a patient to take Nivo/Opdivo or Pembro/Keytruda with various other things, like radiation for example, that allows an anti-PD1 treatment as a first step. Of course there is the nivo/ipi combo…most effective thing going…but with increased risk of side effects, as you noted.
All of these drugs have been shown in multiple studies to work in the brain. There is an ongoing study looking at Pembro in patients with brain mets. All have been found so far…to have approximately the same response rate in the brain as they do in the body. Additionally, many studies are confirming a synergistic effect between all these drugs and radiation. So, hopefully, that will work in your father's favor as well.
You are doing well by your father. Hope this helps. Celeste
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- July 3, 2015 at 4:00 pm
Carrie,
I hope the radiation gets your Dad stable and that he can get a systemic treatment soon.
I've found it it very stressful and frustrating that almost all trials seem to exclude people with brain mets. Usually the trial requires every brain met to be "stable" after treatment which I think means unchanged for at least 30 days, which is a long time to sit around waiting. Other than that, your Dad's lung tumor would allow him to qualify for a clinical trial, whereas if there were no disease outside the brain, I believe that is not the case.
I was given IPI about two weeks after Gamma Knife, which came another two weeks after brain double surgery. There was no disease outside my brain at that time. There were two smaller mets that I understand were too smal and/or hard to get to with surgery, and/or I was already getting two different areas removed by surgery anyway, so those were treated with Gamma Knife only. My doctor thinks I almost certainly got benefit from the IPI I got afterwards. I felt very fortunate after that, and I was NED for 2.5 years after.
All in all it seems like the guidelines doctors seem to have to abide by with the brain are way too cautious, given what getting no sysgtemic treatment can mean.
But it's not impossible IPI could benefit your Dad. It would be frustrating and stressful that it usually takes so long to find out if IPI is working.
– Kyle
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- July 3, 2015 at 4:00 pm
Carrie,
I hope the radiation gets your Dad stable and that he can get a systemic treatment soon.
I've found it it very stressful and frustrating that almost all trials seem to exclude people with brain mets. Usually the trial requires every brain met to be "stable" after treatment which I think means unchanged for at least 30 days, which is a long time to sit around waiting. Other than that, your Dad's lung tumor would allow him to qualify for a clinical trial, whereas if there were no disease outside the brain, I believe that is not the case.
I was given IPI about two weeks after Gamma Knife, which came another two weeks after brain double surgery. There was no disease outside my brain at that time. There were two smaller mets that I understand were too smal and/or hard to get to with surgery, and/or I was already getting two different areas removed by surgery anyway, so those were treated with Gamma Knife only. My doctor thinks I almost certainly got benefit from the IPI I got afterwards. I felt very fortunate after that, and I was NED for 2.5 years after.
All in all it seems like the guidelines doctors seem to have to abide by with the brain are way too cautious, given what getting no sysgtemic treatment can mean.
But it's not impossible IPI could benefit your Dad. It would be frustrating and stressful that it usually takes so long to find out if IPI is working.
– Kyle
-
- July 3, 2015 at 4:00 pm
Carrie,
I hope the radiation gets your Dad stable and that he can get a systemic treatment soon.
I've found it it very stressful and frustrating that almost all trials seem to exclude people with brain mets. Usually the trial requires every brain met to be "stable" after treatment which I think means unchanged for at least 30 days, which is a long time to sit around waiting. Other than that, your Dad's lung tumor would allow him to qualify for a clinical trial, whereas if there were no disease outside the brain, I believe that is not the case.
I was given IPI about two weeks after Gamma Knife, which came another two weeks after brain double surgery. There was no disease outside my brain at that time. There were two smaller mets that I understand were too smal and/or hard to get to with surgery, and/or I was already getting two different areas removed by surgery anyway, so those were treated with Gamma Knife only. My doctor thinks I almost certainly got benefit from the IPI I got afterwards. I felt very fortunate after that, and I was NED for 2.5 years after.
All in all it seems like the guidelines doctors seem to have to abide by with the brain are way too cautious, given what getting no sysgtemic treatment can mean.
But it's not impossible IPI could benefit your Dad. It would be frustrating and stressful that it usually takes so long to find out if IPI is working.
– Kyle
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- July 4, 2015 at 9:18 pm
Hi Carrie. I can't add anything but I just want to wish you all the best. Celeste is amazing to take the time to respond so clearly to all our questions. It is a relief to me just reading other ppls posts and her answers. Good luck. I'm sure you will help your dad to full recovery
anne-Louise
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- July 4, 2015 at 9:18 pm
Hi Carrie. I can't add anything but I just want to wish you all the best. Celeste is amazing to take the time to respond so clearly to all our questions. It is a relief to me just reading other ppls posts and her answers. Good luck. I'm sure you will help your dad to full recovery
anne-Louise
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- July 4, 2015 at 9:18 pm
Hi Carrie. I can't add anything but I just want to wish you all the best. Celeste is amazing to take the time to respond so clearly to all our questions. It is a relief to me just reading other ppls posts and her answers. Good luck. I'm sure you will help your dad to full recovery
anne-Louise
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