50 Gene Panel and NRAS

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  • Post
    • January 20, 2015 at 9:53 pm
    AshleyS
    Participant

      Hey folks,

      My doc recently received the results from my 50 gene panel. I already knew I was BRAF wild, but the panel showed I do have a NRAS mutation. what questions should I ask about this? Any other advice? Thanks!

      Ashley

    Viewing 8 reply threads
    • Replies
        • January 21, 2015 at 1:24 pm
        Bubbles
        Participant

          Hey Ashley,

          I would certainly be asking about MEK 162, now called Binimetinib.  Here's some of the early info:

          http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/01/better-news-for-mek-and-brafmek-combos.html

          http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/06/pretty-darn-impressivea-chat-between.html

          In the last post, specifically this:  Targeted therapies
          Weber:  I was very impressed with Sosman's presentation of the CDK-4 inhibitor combined with the MEK inhibitor 162…a 33% response rate, …phase 1 study with only 22 patients….Nonetheless, the NRAS-mutated population – which are BRAF wild-type because the 2 mutations are mutually exclusive – was a relatively hopeless cohort in terms of targeted therapy, and now it looks like there will be a useful and efficacious targeted therapy for at least 15% of melanoma patients who are NRAS-mutated BRAF wild-type. 

          Sosman is at Vanderbilt in Nashville.  Several studies wth MEK162 are ongoing.  I wish you my best.  C

          • January 21, 2015 at 1:24 pm
          Bubbles
          Participant

            Hey Ashley,

            I would certainly be asking about MEK 162, now called Binimetinib.  Here's some of the early info:

            http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/01/better-news-for-mek-and-brafmek-combos.html

            http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/06/pretty-darn-impressivea-chat-between.html

            In the last post, specifically this:  Targeted therapies
            Weber:  I was very impressed with Sosman's presentation of the CDK-4 inhibitor combined with the MEK inhibitor 162…a 33% response rate, …phase 1 study with only 22 patients….Nonetheless, the NRAS-mutated population – which are BRAF wild-type because the 2 mutations are mutually exclusive – was a relatively hopeless cohort in terms of targeted therapy, and now it looks like there will be a useful and efficacious targeted therapy for at least 15% of melanoma patients who are NRAS-mutated BRAF wild-type. 

            Sosman is at Vanderbilt in Nashville.  Several studies wth MEK162 are ongoing.  I wish you my best.  C

            • January 21, 2015 at 1:24 pm
            Bubbles
            Participant

              Hey Ashley,

              I would certainly be asking about MEK 162, now called Binimetinib.  Here's some of the early info:

              http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/01/better-news-for-mek-and-brafmek-combos.html

              http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/06/pretty-darn-impressivea-chat-between.html

              In the last post, specifically this:  Targeted therapies
              Weber:  I was very impressed with Sosman's presentation of the CDK-4 inhibitor combined with the MEK inhibitor 162…a 33% response rate, …phase 1 study with only 22 patients….Nonetheless, the NRAS-mutated population – which are BRAF wild-type because the 2 mutations are mutually exclusive – was a relatively hopeless cohort in terms of targeted therapy, and now it looks like there will be a useful and efficacious targeted therapy for at least 15% of melanoma patients who are NRAS-mutated BRAF wild-type. 

              Sosman is at Vanderbilt in Nashville.  Several studies wth MEK162 are ongoing.  I wish you my best.  C

              • January 21, 2015 at 7:21 pm
              kylez
              Participant

                Ashley, if you don't mind me asking, what was the specific NRAS mutation they found? I'm curious, mine is "G12A". But there are at least a few different ones besides that. The test for me was done back in 2011, so it wasn't the new test you had. I think it was something special that UCSF did at that time, sequencing patient's tumor samples.

                You can ask if there are any specific therapies targeting NRAS mutations they are aware of, or lacking that, what therapies he recommends for wild type (likely the immune therapies). There's not very much I know about NRAS other than it's been identified as a oncogene driver for melanoma. There are just a very few trials I remember seeing that are testing drug combinations specifically for patients with NRAS-positive tumors. Here's one, this might be the one Celeste is referring to. Other than that, an article or two about the impact of NRAS mutations on overall prognosis. One said prognosis is a little worse for NRAS patients, possibly because (this is me reading into it) there aren't targeted drugs yet like there are for BRAF positive patients. Another was about NRAS-positive patients doing better on high-dose IL2 than non-NRAS patients. I don't think newer immune therapies were included in that assessment/study, guessing perhaps the data is not there or hasn't been analyzed yet.

                Good luck with your upcoming doctor appointment! -Kyle

                 
                  • January 21, 2015 at 7:22 pm
                  kylez
                  Participant

                    (she or he, that is…)

                    • January 21, 2015 at 7:22 pm
                    kylez
                    Participant

                      (she or he, that is…)

                      • January 21, 2015 at 7:22 pm
                      kylez
                      Participant

                        (she or he, that is…)

                      • January 21, 2015 at 7:21 pm
                      kylez
                      Participant

                        Ashley, if you don't mind me asking, what was the specific NRAS mutation they found? I'm curious, mine is "G12A". But there are at least a few different ones besides that. The test for me was done back in 2011, so it wasn't the new test you had. I think it was something special that UCSF did at that time, sequencing patient's tumor samples.

                        You can ask if there are any specific therapies targeting NRAS mutations they are aware of, or lacking that, what therapies he recommends for wild type (likely the immune therapies). There's not very much I know about NRAS other than it's been identified as a oncogene driver for melanoma. There are just a very few trials I remember seeing that are testing drug combinations specifically for patients with NRAS-positive tumors. Here's one, this might be the one Celeste is referring to. Other than that, an article or two about the impact of NRAS mutations on overall prognosis. One said prognosis is a little worse for NRAS patients, possibly because (this is me reading into it) there aren't targeted drugs yet like there are for BRAF positive patients. Another was about NRAS-positive patients doing better on high-dose IL2 than non-NRAS patients. I don't think newer immune therapies were included in that assessment/study, guessing perhaps the data is not there or hasn't been analyzed yet.

                        Good luck with your upcoming doctor appointment! -Kyle

                         
                        • January 21, 2015 at 7:21 pm
                        kylez
                        Participant

                          Ashley, if you don't mind me asking, what was the specific NRAS mutation they found? I'm curious, mine is "G12A". But there are at least a few different ones besides that. The test for me was done back in 2011, so it wasn't the new test you had. I think it was something special that UCSF did at that time, sequencing patient's tumor samples.

                          You can ask if there are any specific therapies targeting NRAS mutations they are aware of, or lacking that, what therapies he recommends for wild type (likely the immune therapies). There's not very much I know about NRAS other than it's been identified as a oncogene driver for melanoma. There are just a very few trials I remember seeing that are testing drug combinations specifically for patients with NRAS-positive tumors. Here's one, this might be the one Celeste is referring to. Other than that, an article or two about the impact of NRAS mutations on overall prognosis. One said prognosis is a little worse for NRAS patients, possibly because (this is me reading into it) there aren't targeted drugs yet like there are for BRAF positive patients. Another was about NRAS-positive patients doing better on high-dose IL2 than non-NRAS patients. I don't think newer immune therapies were included in that assessment/study, guessing perhaps the data is not there or hasn't been analyzed yet.

                          Good luck with your upcoming doctor appointment! -Kyle

                           
                          • January 21, 2015 at 7:42 pm
                          Bubbles
                          Participant

                            And…a point you all may already know….BRAF status doesn't seem to make responses any better or worse when it comes to immunotherapy….Nivo/Opdivo, Keytruda, or Ipi/Yervoy or any combination.  This is out of ASCO, June 2014:

                            Survival, response duration, and activity by BRAF mutation status of nivolumab (anti-PD1, BMS-936588) and ipilimumab concurrent therapy in advanced melanoma
                            Abstract LBA9003

                            Sznol, Kluger, Kirkwood, Wolchok, et al

                            53 melanoma patients were enrolled from 2009-2012 and were given ipi and nivo concurrently, then followed by nivo alone (with a variety of dosing patterns). Patients with and without BRAF had similar response. 
                             

                            NIVO (mg/kg) +
                            IPI (mg/kg) [n]                            		 1-Y OS rate,
                            % [pts at risk]                            		 Median
                            OS, mo                            		 ACAR,
                            %                            		 ACAR by BRAF
                            MT status,* % [n]
                            Pos Neg Unk
                            0.3 + 3 [14] 56 [7] 14.8 57 50 [4] 67 [3] 57 [7]
                            1 + 3 [17] 94 [13] NR 65 50 [2] 50 [6] 78 [9]
                            3 + 1 [16] 89 [3] NR 81 67 [3] 85 [13] – [0]
                            3 + 3 [6] 100 [5] NR 83 100 [1] 75 [4] 100 [1]
                            Concurrent [53] 82 [28] 39.7 70 60 [10] 73 [26] 71 [17]
                            Sequenced† [32] Insufficient
                            followup                            		 13.0 44 44 [9] 47 [15] 38 [8]

                             So with ipi and nivo, combo or alone, BRAF status doesn't seem to affect response.

                             

                            If it helps….C

                            • January 21, 2015 at 7:42 pm
                            Bubbles
                            Participant

                              And…a point you all may already know….BRAF status doesn't seem to make responses any better or worse when it comes to immunotherapy….Nivo/Opdivo, Keytruda, or Ipi/Yervoy or any combination.  This is out of ASCO, June 2014:

                              Survival, response duration, and activity by BRAF mutation status of nivolumab (anti-PD1, BMS-936588) and ipilimumab concurrent therapy in advanced melanoma
                              Abstract LBA9003

                              Sznol, Kluger, Kirkwood, Wolchok, et al

                              53 melanoma patients were enrolled from 2009-2012 and were given ipi and nivo concurrently, then followed by nivo alone (with a variety of dosing patterns). Patients with and without BRAF had similar response. 
                               

                              NIVO (mg/kg) +
                              IPI (mg/kg) [n]                              		 1-Y OS rate,
                              % [pts at risk]                              		 Median
                              OS, mo                              		 ACAR,
                              %                              		 ACAR by BRAF
                              MT status,* % [n]
                              Pos Neg Unk
                              0.3 + 3 [14] 56 [7] 14.8 57 50 [4] 67 [3] 57 [7]
                              1 + 3 [17] 94 [13] NR 65 50 [2] 50 [6] 78 [9]
                              3 + 1 [16] 89 [3] NR 81 67 [3] 85 [13] – [0]
                              3 + 3 [6] 100 [5] NR 83 100 [1] 75 [4] 100 [1]
                              Concurrent [53] 82 [28] 39.7 70 60 [10] 73 [26] 71 [17]
                              Sequenced† [32] Insufficient
                              followup                              		 13.0 44 44 [9] 47 [15] 38 [8]

                               So with ipi and nivo, combo or alone, BRAF status doesn't seem to affect response.

                               

                              If it helps….C

                              • January 21, 2015 at 7:42 pm
                              Bubbles
                              Participant

                                And…a point you all may already know….BRAF status doesn't seem to make responses any better or worse when it comes to immunotherapy….Nivo/Opdivo, Keytruda, or Ipi/Yervoy or any combination.  This is out of ASCO, June 2014:

                                Survival, response duration, and activity by BRAF mutation status of nivolumab (anti-PD1, BMS-936588) and ipilimumab concurrent therapy in advanced melanoma
                                Abstract LBA9003

                                Sznol, Kluger, Kirkwood, Wolchok, et al

                                53 melanoma patients were enrolled from 2009-2012 and were given ipi and nivo concurrently, then followed by nivo alone (with a variety of dosing patterns). Patients with and without BRAF had similar response. 
                                 

                                NIVO (mg/kg) +
                                IPI (mg/kg) [n]                                		 1-Y OS rate,
                                % [pts at risk]                                		 Median
                                OS, mo                                		 ACAR,
                                %                                		 ACAR by BRAF
                                MT status,* % [n]
                                Pos Neg Unk
                                0.3 + 3 [14] 56 [7] 14.8 57 50 [4] 67 [3] 57 [7]
                                1 + 3 [17] 94 [13] NR 65 50 [2] 50 [6] 78 [9]
                                3 + 1 [16] 89 [3] NR 81 67 [3] 85 [13] – [0]
                                3 + 3 [6] 100 [5] NR 83 100 [1] 75 [4] 100 [1]
                                Concurrent [53] 82 [28] 39.7 70 60 [10] 73 [26] 71 [17]
                                Sequenced† [32] Insufficient
                                followup                                		 13.0 44 44 [9] 47 [15] 38 [8]

                                 So with ipi and nivo, combo or alone, BRAF status doesn't seem to affect response.

                                 

                                If it helps….C

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