Combination Therapies

Hey Mark,

You are right in that this combo is very new.  I have not done it nor have I heard any results yet, personal or otherwise.  Not to say there aren't some particepating folks out there and hopefully some will answer.  However, I thought this review from some melanoma big dogs might interest you if you are considering participation.  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/11/review-of-immunotherapy-and-durable.html

Specifically: ". ..current data suggest…Limitations with immunotherapies for some [are] low response rates, delayed onset of effect, toxicity that must be managed carefully, and [it is] difficult to predict which patients will respond…but treatment-free survival and durable responses are possible.  Targeted therapies have: high response rates, side effects usually reversible with dose adjustment…but…require continuous twice daily dosing, may elicit resistance within 6-8 months, and generally do not provide long-lasting benefit after therapy is discontinued.  Strategies that capitalize on the strengths and overcome the weaknesses associated with these treatments are needed and might possibly be achieved through combination and/or sequencing regimens."

Clearly the major melanoma researchers think the BRAF/MEK/anti-PD1 combo is promising.  Weber addresses it as a combo to come at the end of his Paris presentation.

I hope it provides as much help as is hoped with much fewer side effects than when the BRAFi were combined with ipi.  I wish you my best.  Celeste

Hey Mark,

You are right in that this combo is very new.  I have not done it nor have I heard any results yet, personal or otherwise.  Not to say there aren't some particepating folks out there and hopefully some will answer.  However, I thought this review from some melanoma big dogs might interest you if you are considering participation.  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/11/review-of-immunotherapy-and-durable.html

Specifically: ". ..current data suggest…Limitations with immunotherapies for some [are] low response rates, delayed onset of effect, toxicity that must be managed carefully, and [it is] difficult to predict which patients will respond…but treatment-free survival and durable responses are possible.  Targeted therapies have: high response rates, side effects usually reversible with dose adjustment…but…require continuous twice daily dosing, may elicit resistance within 6-8 months, and generally do not provide long-lasting benefit after therapy is discontinued.  Strategies that capitalize on the strengths and overcome the weaknesses associated with these treatments are needed and might possibly be achieved through combination and/or sequencing regimens."

Clearly the major melanoma researchers think the BRAF/MEK/anti-PD1 combo is promising.  Weber addresses it as a combo to come at the end of his Paris presentation.

I hope it provides as much help as is hoped with much fewer side effects than when the BRAFi were combined with ipi.  I wish you my best.  Celeste

Hey Mark,

You are right in that this combo is very new.  I have not done it nor have I heard any results yet, personal or otherwise.  Not to say there aren't some particepating folks out there and hopefully some will answer.  However, I thought this review from some melanoma big dogs might interest you if you are considering participation.  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/11/review-of-immunotherapy-and-durable.html

Specifically: ". ..current data suggest…Limitations with immunotherapies for some [are] low response rates, delayed onset of effect, toxicity that must be managed carefully, and [it is] difficult to predict which patients will respond…but treatment-free survival and durable responses are possible.  Targeted therapies have: high response rates, side effects usually reversible with dose adjustment…but…require continuous twice daily dosing, may elicit resistance within 6-8 months, and generally do not provide long-lasting benefit after therapy is discontinued.  Strategies that capitalize on the strengths and overcome the weaknesses associated with these treatments are needed and might possibly be achieved through combination and/or sequencing regimens."

Clearly the major melanoma researchers think the BRAF/MEK/anti-PD1 combo is promising.  Weber addresses it as a combo to come at the end of his Paris presentation.

I hope it provides as much help as is hoped with much fewer side effects than when the BRAFi were combined with ipi.  I wish you my best.  Celeste

I've been on the mek braf combo then quit that and a week or so later started the keytruda pd1 I'm on now. So no I didn't have all 3 at once.  The combo pills were fairly easy to tolerate for me except at the end which was about week 8 I had 3 days of massive shakes that shook the recliner chills fevers a little throwing up. Before that was not much just high fevers of 103 without me even realizing I had a fever. Technically I could have continued the pills without them knowing while doing the pd1 but I was too afraid so I didn't. Besides for me braf doesn't work I guess because I'm the one in fivish that I guess over stimulate the craf thus still keep the cancer cells alive but the mek was able to keep most stuff from growing. Unlike when I was on zelboraf which did nothing good. Anyway pd1 has been easy to tolerate. Mild fevers that I can easily feel. Early on some grogginess but that went away after 10 days. After around dose 10 I've noticed a constant higher pulse rate. Instead of like 90ish it's very low 100ish like 103 or so. I don't know what the 3 pack would be like but hopefully better than when they tried it with ipi. That was the trial I was supposed to get into in the beginning but didn't and heard the side affects we're really bad. But that was ipi so I hope and think pd1 will prove much better.

Artie

I've been on the mek braf combo then quit that and a week or so later started the keytruda pd1 I'm on now. So no I didn't have all 3 at once.  The combo pills were fairly easy to tolerate for me except at the end which was about week 8 I had 3 days of massive shakes that shook the recliner chills fevers a little throwing up. Before that was not much just high fevers of 103 without me even realizing I had a fever. Technically I could have continued the pills without them knowing while doing the pd1 but I was too afraid so I didn't. Besides for me braf doesn't work I guess because I'm the one in fivish that I guess over stimulate the craf thus still keep the cancer cells alive but the mek was able to keep most stuff from growing. Unlike when I was on zelboraf which did nothing good. Anyway pd1 has been easy to tolerate. Mild fevers that I can easily feel. Early on some grogginess but that went away after 10 days. After around dose 10 I've noticed a constant higher pulse rate. Instead of like 90ish it's very low 100ish like 103 or so. I don't know what the 3 pack would be like but hopefully better than when they tried it with ipi. That was the trial I was supposed to get into in the beginning but didn't and heard the side affects we're really bad. But that was ipi so I hope and think pd1 will prove much better.

Artie

I've been on the mek braf combo then quit that and a week or so later started the keytruda pd1 I'm on now. So no I didn't have all 3 at once.  The combo pills were fairly easy to tolerate for me except at the end which was about week 8 I had 3 days of massive shakes that shook the recliner chills fevers a little throwing up. Before that was not much just high fevers of 103 without me even realizing I had a fever. Technically I could have continued the pills without them knowing while doing the pd1 but I was too afraid so I didn't. Besides for me braf doesn't work I guess because I'm the one in fivish that I guess over stimulate the craf thus still keep the cancer cells alive but the mek was able to keep most stuff from growing. Unlike when I was on zelboraf which did nothing good. Anyway pd1 has been easy to tolerate. Mild fevers that I can easily feel. Early on some grogginess but that went away after 10 days. After around dose 10 I've noticed a constant higher pulse rate. Instead of like 90ish it's very low 100ish like 103 or so. I don't know what the 3 pack would be like but hopefully better than when they tried it with ipi. That was the trial I was supposed to get into in the beginning but didn't and heard the side affects we're really bad. But that was ipi so I hope and think pd1 will prove much better.

Artie

Mark, I've discussed this combo with my onc and it seems promising.  As you've pointed out, very early and no data.  Anecdotally, when ipi was combined with BRAFi and MEKi in a trial, the trial arm with the MEKi was suspended due to side effects (high percentage of colitis).

Mark, I've discussed this combo with my onc and it seems promising.  As you've pointed out, very early and no data.  Anecdotally, when ipi was combined with BRAFi and MEKi in a trial, the trial arm with the MEKi was suspended due to side effects (high percentage of colitis).

Mark, I've discussed this combo with my onc and it seems promising.  As you've pointed out, very early and no data.  Anecdotally, when ipi was combined with BRAFi and MEKi in a trial, the trial arm with the MEKi was suspended due to side effects (high percentage of colitis).

I did zelboraf with great results until a subq came up.  Went on zelboraf with Mekenist for about a month but had to stop for toxicity and moved on to Yervoy.  

I did zelboraf with great results until a subq came up.  Went on zelboraf with Mekenist for about a month but had to stop for toxicity and moved on to Yervoy.  

I did zelboraf with great results until a subq came up.  Went on zelboraf with Mekenist for about a month but had to stop for toxicity and moved on to Yervoy.