The information on this site is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. Content within the patient forum is user-generated and has not been reviewed by medical professionals. Other sections of the Melanoma Research Foundation website include information that has been reviewed by medical professionals as appropriate. All medical decisions should be made in consultation with your doctor or other qualified medical professional.

After Zelboraf

Forums General Melanoma Community After Zelboraf

  • Post
    boot2aboot
    Participant

      Hi to All taking Zelboraf and those who research MM, especially Michael, Charlie, Gene, Dick K and Jimmy B.,

      Hi to All taking Zelboraf and those who research MM, especially Michael, Charlie, Gene, Dick K and Jimmy B.,

      I am currently ending my 4th month of Zelboraf treatment.   I saw the onc and had my second set of scans.  The GOOD news is that my tumors have shrunk 40% and my bloodwork looks good…I have one tumor in my liver measuring .6X.9cm (was.8X1.3 in OCT).  I have one tumor in my spleen which was 1X1cm(was1X1.5 OCT) i have 4 lung mets? nodules the largest being 3m (no change from OCT)… So i would say i had a 40% reduction in my liver and spleen mets…not bad considering i am on a GREATLY reduced dose of Zel due to severe side effects….i was advised to start searching clinical trials because Zelboraf usually quits working after 6 mos…I will head down to Moffitt and consult with Bowtie Guy…

      Here are my questions

      1. is surgery for liver and spleen met a smart way to go? ( the only reason i ask is i have one tumor in each organ and they are small)…but i have no idea what the recovery time will be…and that would be important because i could have no treatment during this time…the lung mets are too small to biopsy and they might not even be mel…but, of course, i will claim they are…because they might be…for stage 4  trials…

      2. If i do surgery can i still get into anti-PD1 trial? or will that boot me out?

      3. If i do surgery should i consider IL-2 instead of PD1?-the only reason i ask this is because IL-2, although it works in 5% of peeps seems to create NED in those it does work…

      4, is any science guy out there currently on to finding a way to target other pathways like CTL4, ect?  Just HOW many pathways is there anyway? other than Braf Mek pathway, PD-1, CTL4?????

      4.instead of anti-PD1 should i consider MEK trial (since i am Braf +)

      Happy Melanoma Free and New EFFECTIVE TREATMENT 2012 everyone…We lost a lot of Great People this year and i don't want to lose anyone else , including me to MM.

      Boots

    Viewing 5 reply threads
    • Replies
        lhaley
        Participant

          Boots,

          I don't have any suggestions but I just wanted to let you know that I hope you continue to have success with shrinkage.

          In the past I have had surgery, my scans are this coming Tuesday. My oncologist has agreed in my past as long as I haven't shown progression when it's only one time and gives me 6 months before I have shown it again. I'm not sure how your Dr might be thinking of 3 different organs.  You might still might want to bring it up.  

          Dealing with my brain met I am now weaning the steroids on Friday to .5.  My fear is that I need to start something systemic and I know that it needs to be totally weaned first. 

          Have a happy New Years!

          Linda

          lhaley
          Participant

            Boots,

            I don't have any suggestions but I just wanted to let you know that I hope you continue to have success with shrinkage.

            In the past I have had surgery, my scans are this coming Tuesday. My oncologist has agreed in my past as long as I haven't shown progression when it's only one time and gives me 6 months before I have shown it again. I'm not sure how your Dr might be thinking of 3 different organs.  You might still might want to bring it up.  

            Dealing with my brain met I am now weaning the steroids on Friday to .5.  My fear is that I need to start something systemic and I know that it needs to be totally weaned first. 

            Have a happy New Years!

            Linda

              jim Breitfeller
              Participant

                Boots, Since you are responding to the BRAF therapy, you may want to see if you qualify for a MEK and or ERK or a combination of.

                The potential for BRAF V600 inhibitors in advanced cutaneous melanoma: rationale and latest evidence

                1. Charlotte Lemech [email protected]

                  1. Sarah Cannon Research UK, London; University College London, London, UK
                2. Jeffrey Infante

                  1. Sarah Cannon Research Institute, Nashville, TN, USA
                3. Hendrik-Tobias Arkenau

                  1. Sarah Cannon Research UK, London; University College London, London, UK

                Abstract

                Historically, patients with advanced cutaneous melanoma have a poor prognosis and limited treatment options. The discovery of selective v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation as an oncogenic mutation in cutaneous melanoma and the importance of the mitogen-activated protein kinase (MAPK) pathway in its tumourigenesis have changed the treatment paradigm for melanoma. Selective BRAF inhibitors and now MEK inhibitors have demonstrated response rates far higher than standard chemotherapeutic options and we review the phase I–III results for these agents in this article. The understanding of mechanisms of resistance that may occur upstream, downstream, at the BRAF level or bypassing the MAPK pathway provides a platform for rational drug development and combination therapies.

                You may want contact the Paper's author, Dr. Lemech for a copy of the paper

                Therapeutic Advances in Medical Oncology

                 

                best regards

                 

                Jimmy B

                jim Breitfeller
                Participant

                  Boots, Since you are responding to the BRAF therapy, you may want to see if you qualify for a MEK and or ERK or a combination of.

                  The potential for BRAF V600 inhibitors in advanced cutaneous melanoma: rationale and latest evidence

                  1. Charlotte Lemech [email protected]

                    1. Sarah Cannon Research UK, London; University College London, London, UK
                  2. Jeffrey Infante

                    1. Sarah Cannon Research Institute, Nashville, TN, USA
                  3. Hendrik-Tobias Arkenau

                    1. Sarah Cannon Research UK, London; University College London, London, UK

                  Abstract

                  Historically, patients with advanced cutaneous melanoma have a poor prognosis and limited treatment options. The discovery of selective v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation as an oncogenic mutation in cutaneous melanoma and the importance of the mitogen-activated protein kinase (MAPK) pathway in its tumourigenesis have changed the treatment paradigm for melanoma. Selective BRAF inhibitors and now MEK inhibitors have demonstrated response rates far higher than standard chemotherapeutic options and we review the phase I–III results for these agents in this article. The understanding of mechanisms of resistance that may occur upstream, downstream, at the BRAF level or bypassing the MAPK pathway provides a platform for rational drug development and combination therapies.

                  You may want contact the Paper's author, Dr. Lemech for a copy of the paper

                  Therapeutic Advances in Medical Oncology

                   

                  best regards

                   

                  Jimmy B

                  boot2aboot
                  Participant

                    Jim, Happy New Year and i hope it's not our last!!!!

                    i can get into a MEK only trial at my oncs now…but, ERK-MEK combo sounds interesting…the problem is…when MM mutates which way does it normally go in Brafy people??? does it stay on Raf pathway or jump to CTl4? or goodness knows whatever else pathways…that is the million dollar  question so i am back to crap shooting again…and one of the reasons i wanted the existing stuff cut out first…still trying to sort out pathways and how it jumps…need to bone up on all those webinars.  Thank you for your suggestion…i have already spoken to the clinical trial nurse in nashville and i was very impressed that they do a full set of genetic tests on MM…i have ONLY had braf done in Ohio.

                    boots….

                    boot2aboot
                    Participant

                      Jim, Happy New Year and i hope it's not our last!!!!

                      i can get into a MEK only trial at my oncs now…but, ERK-MEK combo sounds interesting…the problem is…when MM mutates which way does it normally go in Brafy people??? does it stay on Raf pathway or jump to CTl4? or goodness knows whatever else pathways…that is the million dollar  question so i am back to crap shooting again…and one of the reasons i wanted the existing stuff cut out first…still trying to sort out pathways and how it jumps…need to bone up on all those webinars.  Thank you for your suggestion…i have already spoken to the clinical trial nurse in nashville and i was very impressed that they do a full set of genetic tests on MM…i have ONLY had braf done in Ohio.

                      boots….

                      boot2aboot
                      Participant

                        Jim, Happy New Year and i hope it's not our last!!!!

                        i can get into a MEK only trial at my oncs now…but, ERK-MEK combo sounds interesting…the problem is…when MM mutates which way does it normally go in Brafy people??? does it stay on Raf pathway or jump to CTl4? or goodness knows whatever else pathways…that is the million dollar  question so i am back to crap shooting again…and one of the reasons i wanted the existing stuff cut out first…still trying to sort out pathways and how it jumps…need to bone up on all those webinars.  Thank you for your suggestion…i have already spoken to the clinical trial nurse in nashville and i was very impressed that they do a full set of genetic tests on MM…i have ONLY had braf done in Ohio.

                        boots….

                        jim Breitfeller
                        Participant

                          Boots, Since you are responding to the BRAF therapy, you may want to see if you qualify for a MEK and or ERK or a combination of.

                          The potential for BRAF V600 inhibitors in advanced cutaneous melanoma: rationale and latest evidence

                          1. Charlotte Lemech [email protected]

                            1. Sarah Cannon Research UK, London; University College London, London, UK
                          2. Jeffrey Infante

                            1. Sarah Cannon Research Institute, Nashville, TN, USA
                          3. Hendrik-Tobias Arkenau

                            1. Sarah Cannon Research UK, London; University College London, London, UK

                          Abstract

                          Historically, patients with advanced cutaneous melanoma have a poor prognosis and limited treatment options. The discovery of selective v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation as an oncogenic mutation in cutaneous melanoma and the importance of the mitogen-activated protein kinase (MAPK) pathway in its tumourigenesis have changed the treatment paradigm for melanoma. Selective BRAF inhibitors and now MEK inhibitors have demonstrated response rates far higher than standard chemotherapeutic options and we review the phase I–III results for these agents in this article. The understanding of mechanisms of resistance that may occur upstream, downstream, at the BRAF level or bypassing the MAPK pathway provides a platform for rational drug development and combination therapies.

                          You may want contact the Paper's author, Dr. Lemech for a copy of the paper

                          Therapeutic Advances in Medical Oncology

                           

                          best regards

                           

                          Jimmy B

                        lhaley
                        Participant

                          Boots,

                          I don't have any suggestions but I just wanted to let you know that I hope you continue to have success with shrinkage.

                          In the past I have had surgery, my scans are this coming Tuesday. My oncologist has agreed in my past as long as I haven't shown progression when it's only one time and gives me 6 months before I have shown it again. I'm not sure how your Dr might be thinking of 3 different organs.  You might still might want to bring it up.  

                          Dealing with my brain met I am now weaning the steroids on Friday to .5.  My fear is that I need to start something systemic and I know that it needs to be totally weaned first. 

                          Have a happy New Years!

                          Linda

                          Charlie S
                          Participant

                            Hey there Boots.  

                            About surgery and IL2, I'm including a video link of a talk my surgical onc gave about surgery and the role of IL-2 in the era of Yervoy and Zelboraf at a recent Aim at Melanoma Conference  http://www.youtube.com/watch?v=gOUtIy6T4oM&feature=relmfu..  The audio is a bit weak, so crank up the speakers. So,basically yes, surgery is an option and IL2 is an option, although many trials require measurable disease, few if any rule you out for either surgery or prior IL2 use.

                            And here is a link to a pretty up-to-date listing of the anti-PD1 trials and the exclusions. http://www.m-icab.org/images/stories/M-ICAB_table_-_final_small.pdf,  skip the first listed worthless link.  In essence, two weeks out from surgery prior to receiving trial drug.  

                            Of note, many of these PD1 trials exclude prior use of Yervoy, many want an HLA typing of HLA-A02/HLA-A-0201 and many want either/or/and  Melan-A, HMB-45, NY-ESO-1 positive tumors, but there is trial that looks at Zelboraf following IPI, go figure. So if you are even considering a future trial, it would be worthwhile now to see how you stack up for those qualifiers.

                            There are a slew of signaling pathways and a slew of them are being studied; but there is mounting evidence that Braf+ can yield some sensitivity to MEK pathways as well. The problem with pathways is they all have built in redudancies; that is to say though one pathway signal can be blocked, as is the case with V600, each pathway has built in mechanisms to re- route to another pathway, which is why Zelboraf has short term success.  Here is another video link from the same conference that discusses signaling pathways http://www.youtube.com/watch?v=BhUXRmLdlvM&feature=relmfu

                            It is also worthwhile to look at Jerry from Fauq recent post  anti-CTLA-4 and Anti-PD-1 antibody

                            Because I am a fan of IL2,, I found it interesting that in a recent study about PD1 cells http://onlinelibrary.wiley.com/doi/10.1002/eji.201040959/abstract,, it was found  that they actually produce IL2.  If that is true, it might follow that IL2 could help if you later did get into a PDI trial.  Only an opinion.

                            Lastly, here is a link for an interesting trial for liver mets at MDA that you might find interesting http://www.clinicaltrials.gov/ct2/show/NCT00833807?cond=%22Melanoma%22&rank=185

                            Probably waaaaaaaaaaaaay more information than you wanted and as always take what you want and leave the rest !

                            Cheers,

                            Charlie S

                              boot2aboot
                              Participant

                                Information is always good, Charlie, and thank you for your input…i know you and King had good success with surgery ….i am leaning on moving down raf pathway suggested by you and Jim …just am stuck between that and PD 1 trials because the initial success rates and i need to study the info on Mek trials better…i know braf jumps to mek jumps to who knows where…thank you…i will post my decision when i make one…

                                boots 

                                boot2aboot
                                Participant

                                  Information is always good, Charlie, and thank you for your input…i know you and King had good success with surgery ….i am leaning on moving down raf pathway suggested by you and Jim …just am stuck between that and PD 1 trials because the initial success rates and i need to study the info on Mek trials better…i know braf jumps to mek jumps to who knows where…thank you…i will post my decision when i make one…

                                  boots 

                                  NYKaren
                                  Participant

                                    Hey, Boots,

                                    No advice/info from me, you know wayyyy more than I do.

                                    Just sending good thoughts your way.

                                    take care,

                                    karen

                                    NYKaren
                                    Participant

                                      Hey, Boots,

                                      No advice/info from me, you know wayyyy more than I do.

                                      Just sending good thoughts your way.

                                      take care,

                                      karen

                                      NYKaren
                                      Participant

                                        Hey, Boots,

                                        No advice/info from me, you know wayyyy more than I do.

                                        Just sending good thoughts your way.

                                        take care,

                                        karen

                                        boot2aboot
                                        Participant

                                          Information is always good, Charlie, and thank you for your input…i know you and King had good success with surgery ….i am leaning on moving down raf pathway suggested by you and Jim …just am stuck between that and PD 1 trials because the initial success rates and i need to study the info on Mek trials better…i know braf jumps to mek jumps to who knows where…thank you…i will post my decision when i make one…

                                          boots 

                                        Charlie S
                                        Participant

                                          Hey there Boots.  

                                          About surgery and IL2, I'm including a video link of a talk my surgical onc gave about surgery and the role of IL-2 in the era of Yervoy and Zelboraf at a recent Aim at Melanoma Conference  http://www.youtube.com/watch?v=gOUtIy6T4oM&feature=relmfu..  The audio is a bit weak, so crank up the speakers. So,basically yes, surgery is an option and IL2 is an option, although many trials require measurable disease, few if any rule you out for either surgery or prior IL2 use.

                                          And here is a link to a pretty up-to-date listing of the anti-PD1 trials and the exclusions. http://www.m-icab.org/images/stories/M-ICAB_table_-_final_small.pdf,  skip the first listed worthless link.  In essence, two weeks out from surgery prior to receiving trial drug.  

                                          Of note, many of these PD1 trials exclude prior use of Yervoy, many want an HLA typing of HLA-A02/HLA-A-0201 and many want either/or/and  Melan-A, HMB-45, NY-ESO-1 positive tumors, but there is trial that looks at Zelboraf following IPI, go figure. So if you are even considering a future trial, it would be worthwhile now to see how you stack up for those qualifiers.

                                          There are a slew of signaling pathways and a slew of them are being studied; but there is mounting evidence that Braf+ can yield some sensitivity to MEK pathways as well. The problem with pathways is they all have built in redudancies; that is to say though one pathway signal can be blocked, as is the case with V600, each pathway has built in mechanisms to re- route to another pathway, which is why Zelboraf has short term success.  Here is another video link from the same conference that discusses signaling pathways http://www.youtube.com/watch?v=BhUXRmLdlvM&feature=relmfu

                                          It is also worthwhile to look at Jerry from Fauq recent post  anti-CTLA-4 and Anti-PD-1 antibody

                                          Because I am a fan of IL2,, I found it interesting that in a recent study about PD1 cells http://onlinelibrary.wiley.com/doi/10.1002/eji.201040959/abstract,, it was found  that they actually produce IL2.  If that is true, it might follow that IL2 could help if you later did get into a PDI trial.  Only an opinion.

                                          Lastly, here is a link for an interesting trial for liver mets at MDA that you might find interesting http://www.clinicaltrials.gov/ct2/show/NCT00833807?cond=%22Melanoma%22&rank=185

                                          Probably waaaaaaaaaaaaay more information than you wanted and as always take what you want and leave the rest !

                                          Cheers,

                                          Charlie S

                                          Charlie S
                                          Participant

                                            Hey there Boots.  

                                            About surgery and IL2, I'm including a video link of a talk my surgical onc gave about surgery and the role of IL-2 in the era of Yervoy and Zelboraf at a recent Aim at Melanoma Conference  http://www.youtube.com/watch?v=gOUtIy6T4oM&feature=relmfu..  The audio is a bit weak, so crank up the speakers. So,basically yes, surgery is an option and IL2 is an option, although many trials require measurable disease, few if any rule you out for either surgery or prior IL2 use.

                                            And here is a link to a pretty up-to-date listing of the anti-PD1 trials and the exclusions. http://www.m-icab.org/images/stories/M-ICAB_table_-_final_small.pdf,  skip the first listed worthless link.  In essence, two weeks out from surgery prior to receiving trial drug.  

                                            Of note, many of these PD1 trials exclude prior use of Yervoy, many want an HLA typing of HLA-A02/HLA-A-0201 and many want either/or/and  Melan-A, HMB-45, NY-ESO-1 positive tumors, but there is trial that looks at Zelboraf following IPI, go figure. So if you are even considering a future trial, it would be worthwhile now to see how you stack up for those qualifiers.

                                            There are a slew of signaling pathways and a slew of them are being studied; but there is mounting evidence that Braf+ can yield some sensitivity to MEK pathways as well. The problem with pathways is they all have built in redudancies; that is to say though one pathway signal can be blocked, as is the case with V600, each pathway has built in mechanisms to re- route to another pathway, which is why Zelboraf has short term success.  Here is another video link from the same conference that discusses signaling pathways http://www.youtube.com/watch?v=BhUXRmLdlvM&feature=relmfu

                                            It is also worthwhile to look at Jerry from Fauq recent post  anti-CTLA-4 and Anti-PD-1 antibody

                                            Because I am a fan of IL2,, I found it interesting that in a recent study about PD1 cells http://onlinelibrary.wiley.com/doi/10.1002/eji.201040959/abstract,, it was found  that they actually produce IL2.  If that is true, it might follow that IL2 could help if you later did get into a PDI trial.  Only an opinion.

                                            Lastly, here is a link for an interesting trial for liver mets at MDA that you might find interesting http://www.clinicaltrials.gov/ct2/show/NCT00833807?cond=%22Melanoma%22&rank=185

                                            Probably waaaaaaaaaaaaay more information than you wanted and as always take what you want and leave the rest !

                                            Cheers,

                                            Charlie S

                                        Viewing 5 reply threads
                                        • You must be logged in to reply to this topic.
                                        About the MRF Patient Forum

                                        The MRF Patient Forum is the oldest and largest online community of people affected by melanoma. It is designed to provide peer support and information to caregivers, patients, family and friends. There is no better place to discuss different parts of your journey with this cancer and find the friends and support resources to make that journey more bearable.

                                        The information on the forum is open and accessible to everyone. To add a new topic or to post a reply, you must be a registered user. Please note that you will be able to post both topics and replies anonymously even though you are logged in. All posts must abide by MRF posting policies.