BRAF Mutation

Forums General Melanoma Community BRAF Mutation

  • Post
    JoshF
    Participant
      One thing I didn’t mention was that BRAF tests came back negative. I’m not sure whether that’s a good thing or bad thing. Can someone shed light on this? I know it excludes someone who is braf negative from many treatments but don’t understand it much outside of that.
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    • Replies
        DeniseK
        Participant

          Hey Josh,

          I think there's only 2 drugs Zelboraf and Dabrafenib you wouldn't be able to take.  These are both basicially the same BRAF inhibitors.  Zelboraf only worked 6 months for me.  If I'm not mistaken you could still do MEK inhibitor which my specialist explained is a deeper protein in the tumors, maybe that's why it's working so well for me??!  Are you doing any treatment?  Maybe look into some trials for immontherapy.  I did interferon for 2-1/2 weeks of high dose before I had to stop but I was stage 2c at that time.  I don't believe it would have worked anyway, but with the newer drugs I would definately look into doing something to stop things from going stage IV.  That's just my opinion/suggestion.

          Where are you located? Getting treatment?

          All my best,

          Denise

            JoshF
            Participant

              Thanks Denise! The first go around I was BRAF neg but oncologist never explained to me, only said that exculdes a patient from certain drugs. I'm hoping tomorrow to find more out tomorrow about treatments but docs keep telling me to slow down so assuming they want to do surgery then discuss treatments. I've heard the horror stories on this site about interferon and sounds like it's success rate is low.

               

              I'm in Chicago. My oncologists are Richards & Hallmeyer at Oncology Specialists. Both regional melanoma experts. My surgery will be done at Northwestern Memorial Hospital. I've been told by other here that travel to get in clinical tirial might be best option. Guess I'll take it one step at a time.

               

              Josh

              POW
              Participant

                Josh, when it's possible, surgery is always the best option for treating melanoma. If you only have one or two mets that can be surgically removed, then they are GONE! You are then considered NED. So it's good that your mets can be surgically removed. 

                BRAF and MEK are two proteins that cause melanoma cells to proliferate without stopping. Theoretically,if you can inhibit those proteins, you can stop the tumors from growing and even kill the tumor cells. Unfortunately, there is no drug that can inhibit the normal (or "wild type") BRAF protein. There are, however, two drugs that can inhibit the BRAF protein if it contains a certain mutation (called the V600E,K mutation). About 50% of melanomas contain that mutation, so those patients might benefit from taking a BRAF inhibitor. Those inhibitors are called vemurafenib (trade name Zelboraf) and dabarafenib (trade name Tafinlar).

                When these BRAF drugs work (in about 50% of the people who take them) they work quickly and well– shrinking tumors within a few weeks. Unfortunately, most melanoma cells eventually become resistant to the BRAF inibitors within 6-9 months, so the good effects don't last very long. And, of course, there are some nasty side effects. Therefore, the BRAF inhibitors are usually used as a short-term "emergency" meaasure in people with severe and/or rapidly spreading Stage IV melanoma. You're not nearly there, and you may never be there.

                There are a couple of other inhibitors for MEK, the other proliferative protein. The one that was just recently approved by the FDA is called trametinib (tracde name Mekinist). You do not need to have any mutations to take MEK inhibitors. It does stop and/or kill melanoma in some patients, but not in as many people as the BRAF inhibitors do. What the doctors have learned over the last few years is that taking both a BRAF inhibitor and a MEK inhibitor at the same time works like a 1-2 punch against melanoma. The combination works better than either drug alone. Denise had that exact experience. 

                Again, melanoma cells can become resistant to MEK inhibitors and the drugs have side effects, so they are usually only used in advanced Stage IV cases.  

                So the bottom line for you is that you do not need either of these drugs right now. You may never need them. Since you do not have the BRAFmutation, neither Zelborf nor Tafinlar would do you any good, anyway, but the MEK inhibitor might. The immune-based treatments like ipi (Yervoy) and anti-PD1 (now in the FDA approval process) offer more promise for long-term efficacy. They are being used for Stage IV patients and sometimes for Stage III patients who are at a high risk for a recurrence. You are not there yet, either.

                But if you ever have another local recurrence or if you do someday develop a distant recurrence (making you Stage IV), it is reassuring to know that both ipi and (probably) anti-PD1 will be available for you. And, if you ever need it, MEK will be available to you, too. And all of those treatments have only been available for the last 2 or 3 years, so in a way yo are lucky. (And, yes, having a "glass half full" attitude is very helpful to melanoma patients!).

                JoshF
                Participant

                  Great explanation…thank you immensly! Does having BRAF mutation change a prognosis? I guess if you have the BRAF mutation is the melanoma more aggressive?

                  POW
                  Participant

                    Nope. No relationship that I know of. A BRAF mutation (or rather, the CORRECT BRAF mutation) only indicates whether or not you are likely to benefit from taking vemurafenib or dabrafenib.

                    POW
                    Participant

                      Nope. No relationship that I know of. A BRAF mutation (or rather, the CORRECT BRAF mutation) only indicates whether or not you are likely to benefit from taking vemurafenib or dabrafenib.

                      POW
                      Participant

                        Nope. No relationship that I know of. A BRAF mutation (or rather, the CORRECT BRAF mutation) only indicates whether or not you are likely to benefit from taking vemurafenib or dabrafenib.

                        JoshF
                        Participant

                          Great explanation…thank you immensly! Does having BRAF mutation change a prognosis? I guess if you have the BRAF mutation is the melanoma more aggressive?

                          JoshF
                          Participant

                            Great explanation…thank you immensly! Does having BRAF mutation change a prognosis? I guess if you have the BRAF mutation is the melanoma more aggressive?

                            POW
                            Participant

                              Josh, when it's possible, surgery is always the best option for treating melanoma. If you only have one or two mets that can be surgically removed, then they are GONE! You are then considered NED. So it's good that your mets can be surgically removed. 

                              BRAF and MEK are two proteins that cause melanoma cells to proliferate without stopping. Theoretically,if you can inhibit those proteins, you can stop the tumors from growing and even kill the tumor cells. Unfortunately, there is no drug that can inhibit the normal (or "wild type") BRAF protein. There are, however, two drugs that can inhibit the BRAF protein if it contains a certain mutation (called the V600E,K mutation). About 50% of melanomas contain that mutation, so those patients might benefit from taking a BRAF inhibitor. Those inhibitors are called vemurafenib (trade name Zelboraf) and dabarafenib (trade name Tafinlar).

                              When these BRAF drugs work (in about 50% of the people who take them) they work quickly and well– shrinking tumors within a few weeks. Unfortunately, most melanoma cells eventually become resistant to the BRAF inibitors within 6-9 months, so the good effects don't last very long. And, of course, there are some nasty side effects. Therefore, the BRAF inhibitors are usually used as a short-term "emergency" meaasure in people with severe and/or rapidly spreading Stage IV melanoma. You're not nearly there, and you may never be there.

                              There are a couple of other inhibitors for MEK, the other proliferative protein. The one that was just recently approved by the FDA is called trametinib (tracde name Mekinist). You do not need to have any mutations to take MEK inhibitors. It does stop and/or kill melanoma in some patients, but not in as many people as the BRAF inhibitors do. What the doctors have learned over the last few years is that taking both a BRAF inhibitor and a MEK inhibitor at the same time works like a 1-2 punch against melanoma. The combination works better than either drug alone. Denise had that exact experience. 

                              Again, melanoma cells can become resistant to MEK inhibitors and the drugs have side effects, so they are usually only used in advanced Stage IV cases.  

                              So the bottom line for you is that you do not need either of these drugs right now. You may never need them. Since you do not have the BRAFmutation, neither Zelborf nor Tafinlar would do you any good, anyway, but the MEK inhibitor might. The immune-based treatments like ipi (Yervoy) and anti-PD1 (now in the FDA approval process) offer more promise for long-term efficacy. They are being used for Stage IV patients and sometimes for Stage III patients who are at a high risk for a recurrence. You are not there yet, either.

                              But if you ever have another local recurrence or if you do someday develop a distant recurrence (making you Stage IV), it is reassuring to know that both ipi and (probably) anti-PD1 will be available for you. And, if you ever need it, MEK will be available to you, too. And all of those treatments have only been available for the last 2 or 3 years, so in a way yo are lucky. (And, yes, having a "glass half full" attitude is very helpful to melanoma patients!).

                              POW
                              Participant

                                Josh, when it's possible, surgery is always the best option for treating melanoma. If you only have one or two mets that can be surgically removed, then they are GONE! You are then considered NED. So it's good that your mets can be surgically removed. 

                                BRAF and MEK are two proteins that cause melanoma cells to proliferate without stopping. Theoretically,if you can inhibit those proteins, you can stop the tumors from growing and even kill the tumor cells. Unfortunately, there is no drug that can inhibit the normal (or "wild type") BRAF protein. There are, however, two drugs that can inhibit the BRAF protein if it contains a certain mutation (called the V600E,K mutation). About 50% of melanomas contain that mutation, so those patients might benefit from taking a BRAF inhibitor. Those inhibitors are called vemurafenib (trade name Zelboraf) and dabarafenib (trade name Tafinlar).

                                When these BRAF drugs work (in about 50% of the people who take them) they work quickly and well– shrinking tumors within a few weeks. Unfortunately, most melanoma cells eventually become resistant to the BRAF inibitors within 6-9 months, so the good effects don't last very long. And, of course, there are some nasty side effects. Therefore, the BRAF inhibitors are usually used as a short-term "emergency" meaasure in people with severe and/or rapidly spreading Stage IV melanoma. You're not nearly there, and you may never be there.

                                There are a couple of other inhibitors for MEK, the other proliferative protein. The one that was just recently approved by the FDA is called trametinib (tracde name Mekinist). You do not need to have any mutations to take MEK inhibitors. It does stop and/or kill melanoma in some patients, but not in as many people as the BRAF inhibitors do. What the doctors have learned over the last few years is that taking both a BRAF inhibitor and a MEK inhibitor at the same time works like a 1-2 punch against melanoma. The combination works better than either drug alone. Denise had that exact experience. 

                                Again, melanoma cells can become resistant to MEK inhibitors and the drugs have side effects, so they are usually only used in advanced Stage IV cases.  

                                So the bottom line for you is that you do not need either of these drugs right now. You may never need them. Since you do not have the BRAFmutation, neither Zelborf nor Tafinlar would do you any good, anyway, but the MEK inhibitor might. The immune-based treatments like ipi (Yervoy) and anti-PD1 (now in the FDA approval process) offer more promise for long-term efficacy. They are being used for Stage IV patients and sometimes for Stage III patients who are at a high risk for a recurrence. You are not there yet, either.

                                But if you ever have another local recurrence or if you do someday develop a distant recurrence (making you Stage IV), it is reassuring to know that both ipi and (probably) anti-PD1 will be available for you. And, if you ever need it, MEK will be available to you, too. And all of those treatments have only been available for the last 2 or 3 years, so in a way yo are lucky. (And, yes, having a "glass half full" attitude is very helpful to melanoma patients!).

                                JoshF
                                Participant

                                  Thanks Denise! The first go around I was BRAF neg but oncologist never explained to me, only said that exculdes a patient from certain drugs. I'm hoping tomorrow to find more out tomorrow about treatments but docs keep telling me to slow down so assuming they want to do surgery then discuss treatments. I've heard the horror stories on this site about interferon and sounds like it's success rate is low.

                                   

                                  I'm in Chicago. My oncologists are Richards & Hallmeyer at Oncology Specialists. Both regional melanoma experts. My surgery will be done at Northwestern Memorial Hospital. I've been told by other here that travel to get in clinical tirial might be best option. Guess I'll take it one step at a time.

                                   

                                  Josh

                                  JoshF
                                  Participant

                                    Thanks Denise! The first go around I was BRAF neg but oncologist never explained to me, only said that exculdes a patient from certain drugs. I'm hoping tomorrow to find more out tomorrow about treatments but docs keep telling me to slow down so assuming they want to do surgery then discuss treatments. I've heard the horror stories on this site about interferon and sounds like it's success rate is low.

                                     

                                    I'm in Chicago. My oncologists are Richards & Hallmeyer at Oncology Specialists. Both regional melanoma experts. My surgery will be done at Northwestern Memorial Hospital. I've been told by other here that travel to get in clinical tirial might be best option. Guess I'll take it one step at a time.

                                     

                                    Josh

                                  DeniseK
                                  Participant

                                    Hey Josh,

                                    I think there's only 2 drugs Zelboraf and Dabrafenib you wouldn't be able to take.  These are both basicially the same BRAF inhibitors.  Zelboraf only worked 6 months for me.  If I'm not mistaken you could still do MEK inhibitor which my specialist explained is a deeper protein in the tumors, maybe that's why it's working so well for me??!  Are you doing any treatment?  Maybe look into some trials for immontherapy.  I did interferon for 2-1/2 weeks of high dose before I had to stop but I was stage 2c at that time.  I don't believe it would have worked anyway, but with the newer drugs I would definately look into doing something to stop things from going stage IV.  That's just my opinion/suggestion.

                                    Where are you located? Getting treatment?

                                    All my best,

                                    Denise

                                    DeniseK
                                    Participant

                                      Hey Josh,

                                      I think there's only 2 drugs Zelboraf and Dabrafenib you wouldn't be able to take.  These are both basicially the same BRAF inhibitors.  Zelboraf only worked 6 months for me.  If I'm not mistaken you could still do MEK inhibitor which my specialist explained is a deeper protein in the tumors, maybe that's why it's working so well for me??!  Are you doing any treatment?  Maybe look into some trials for immontherapy.  I did interferon for 2-1/2 weeks of high dose before I had to stop but I was stage 2c at that time.  I don't believe it would have worked anyway, but with the newer drugs I would definately look into doing something to stop things from going stage IV.  That's just my opinion/suggestion.

                                      Where are you located? Getting treatment?

                                      All my best,

                                      Denise

                                      JerryfromFauq
                                      Participant

                                        I wouldn't count  it as particular good nor bad.  It is another part of knowledge to have filed away if it is ever needed.  Helps to know what to look at as being more appropriate for  oneself. 

                                        MEK  is in the same signaling pathway as the RAS and RAF signaling, but at a lower level.  The blocking  of the signaling at the BRAF level tends to allow a later activation at the MEK level as melanoma works its way.

                                        http://www.ncbi.nlm.nih.gov/books/NBK10043/figure/A1054/?report=objectonly

                                        http://www.ncbi.nlm.nih.gov/books/NBK10043/#A1053

                                        JerryfromFauq
                                        Participant

                                          I wouldn't count  it as particular good nor bad.  It is another part of knowledge to have filed away if it is ever needed.  Helps to know what to look at as being more appropriate for  oneself. 

                                          MEK  is in the same signaling pathway as the RAS and RAF signaling, but at a lower level.  The blocking  of the signaling at the BRAF level tends to allow a later activation at the MEK level as melanoma works its way.

                                          http://www.ncbi.nlm.nih.gov/books/NBK10043/figure/A1054/?report=objectonly

                                          http://www.ncbi.nlm.nih.gov/books/NBK10043/#A1053

                                          JerryfromFauq
                                          Participant

                                            I wouldn't count  it as particular good nor bad.  It is another part of knowledge to have filed away if it is ever needed.  Helps to know what to look at as being more appropriate for  oneself. 

                                            MEK  is in the same signaling pathway as the RAS and RAF signaling, but at a lower level.  The blocking  of the signaling at the BRAF level tends to allow a later activation at the MEK level as melanoma works its way.

                                            http://www.ncbi.nlm.nih.gov/books/NBK10043/figure/A1054/?report=objectonly

                                            http://www.ncbi.nlm.nih.gov/books/NBK10043/#A1053

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