› Forums › General Melanoma Community › Dabrafenib + Mekinist- how long have they worked for you?
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bonusfries.
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- August 2, 2014 at 11:47 am
I saw a post earlier this week polling people with NED after treatment of stage IV melanoma. So I thought to ask how many of you out there have stable non-progression of Stage IV on this drug combo. My husband has been on it since February with stable disease as of July's scans.
Prior to that he was treated with stereotactic brain radiation surgery x 8 brain tumors on two occasions, Vemurafenib alone, and Vemurafenib + XL888(pre-clinical trial drug) and dabrafenib alone.
His energy level and skin color have returned to his pre stage 4 level on the dabrafenib and Mekinist combo
- Replies
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- August 2, 2014 at 2:10 pm
Sarah, I've been on the GSK combo since last August (started one year ago on this day). I believe that the reported progression free survival median is 10.5 months. In my case, the GSK combo dramatically reduced my tumor burden (let's say ballpark 70%) initially. I've been stable since my February scans. (I also worked-in ipi between December and February.)
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- August 2, 2014 at 2:10 pm
Sarah, I've been on the GSK combo since last August (started one year ago on this day). I believe that the reported progression free survival median is 10.5 months. In my case, the GSK combo dramatically reduced my tumor burden (let's say ballpark 70%) initially. I've been stable since my February scans. (I also worked-in ipi between December and February.)
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- August 2, 2014 at 8:52 pm
Thanks for the speedy reply. My husband has not had any tumor reduction on this combo. However he had significant reduction on the Vemurafenib which he maintained. The Vemurafenib however was too weak a foe for the brain mets and 5 new mets developed after radiation in spite of the Vemurafenib, which is what prompted the change to dabrafenib and Mekinist. So far no new brain mets since October. Seven of the 8 brain mets no longer detectable on MRI.
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- August 2, 2014 at 8:52 pm
Thanks for the speedy reply. My husband has not had any tumor reduction on this combo. However he had significant reduction on the Vemurafenib which he maintained. The Vemurafenib however was too weak a foe for the brain mets and 5 new mets developed after radiation in spite of the Vemurafenib, which is what prompted the change to dabrafenib and Mekinist. So far no new brain mets since October. Seven of the 8 brain mets no longer detectable on MRI.
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- August 2, 2014 at 8:52 pm
Thanks for the speedy reply. My husband has not had any tumor reduction on this combo. However he had significant reduction on the Vemurafenib which he maintained. The Vemurafenib however was too weak a foe for the brain mets and 5 new mets developed after radiation in spite of the Vemurafenib, which is what prompted the change to dabrafenib and Mekinist. So far no new brain mets since October. Seven of the 8 brain mets no longer detectable on MRI.
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- August 4, 2014 at 10:13 am
Hi Mat,
I have also read about the 10.5-month progression-free period for the combo, but the latest data seems to suggest it may be longer (25-month survival):
(From Catherine Poole on MIF)
"We heard from Keith Flaherty,[12] who gave us an update on the BRF-113220 trial. That was the 409-patient, phase 1/2 trial in which the important data were published in 2012 by Keith in the New England Journal of Medicine. [13] I presented these data at ASCO last year.[14] This was a randomized study with 162 patients, of whom 54 received dabrafenib alone (the BRAF inhibitor), 54 received dabrafenib with a lower dose of the MEK inhibitor trametinib, and 54 received dabrafenib and what we hoped was the optimal dose of the MEK inhibitor. The updated data showed a clear superior response rate: 76% vs the mid-50% range for either of the other arms.
The survival data were presented here for the first time. There was a 25-month median survival with a significant tail on the curve. Our institution was the biggest accruer to that trial. About 20% of our patients at years 3-4 are still on treatment and doing well, with many complete responses over time. It is a very impressive treatment. It makes you wonder: Maybe a BRAF-mutated patient who starts on this combination should not receive immunotherapy first. I would like to know what happened to the patients who failed the combination and then went on to immunotherapy. A debate is raging in our field about whether we should give immunotherapy or targeted therapy first, but I can't argue with a 25-month median survival — the best in any phase 2 trial of a significant size that I have ever seen.
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- August 4, 2014 at 10:13 am
Hi Mat,
I have also read about the 10.5-month progression-free period for the combo, but the latest data seems to suggest it may be longer (25-month survival):
(From Catherine Poole on MIF)
"We heard from Keith Flaherty,[12] who gave us an update on the BRF-113220 trial. That was the 409-patient, phase 1/2 trial in which the important data were published in 2012 by Keith in the New England Journal of Medicine. [13] I presented these data at ASCO last year.[14] This was a randomized study with 162 patients, of whom 54 received dabrafenib alone (the BRAF inhibitor), 54 received dabrafenib with a lower dose of the MEK inhibitor trametinib, and 54 received dabrafenib and what we hoped was the optimal dose of the MEK inhibitor. The updated data showed a clear superior response rate: 76% vs the mid-50% range for either of the other arms.
The survival data were presented here for the first time. There was a 25-month median survival with a significant tail on the curve. Our institution was the biggest accruer to that trial. About 20% of our patients at years 3-4 are still on treatment and doing well, with many complete responses over time. It is a very impressive treatment. It makes you wonder: Maybe a BRAF-mutated patient who starts on this combination should not receive immunotherapy first. I would like to know what happened to the patients who failed the combination and then went on to immunotherapy. A debate is raging in our field about whether we should give immunotherapy or targeted therapy first, but I can't argue with a 25-month median survival — the best in any phase 2 trial of a significant size that I have ever seen.
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- August 4, 2014 at 10:13 am
Hi Mat,
I have also read about the 10.5-month progression-free period for the combo, but the latest data seems to suggest it may be longer (25-month survival):
(From Catherine Poole on MIF)
"We heard from Keith Flaherty,[12] who gave us an update on the BRF-113220 trial. That was the 409-patient, phase 1/2 trial in which the important data were published in 2012 by Keith in the New England Journal of Medicine. [13] I presented these data at ASCO last year.[14] This was a randomized study with 162 patients, of whom 54 received dabrafenib alone (the BRAF inhibitor), 54 received dabrafenib with a lower dose of the MEK inhibitor trametinib, and 54 received dabrafenib and what we hoped was the optimal dose of the MEK inhibitor. The updated data showed a clear superior response rate: 76% vs the mid-50% range for either of the other arms.
The survival data were presented here for the first time. There was a 25-month median survival with a significant tail on the curve. Our institution was the biggest accruer to that trial. About 20% of our patients at years 3-4 are still on treatment and doing well, with many complete responses over time. It is a very impressive treatment. It makes you wonder: Maybe a BRAF-mutated patient who starts on this combination should not receive immunotherapy first. I would like to know what happened to the patients who failed the combination and then went on to immunotherapy. A debate is raging in our field about whether we should give immunotherapy or targeted therapy first, but I can't argue with a 25-month median survival — the best in any phase 2 trial of a significant size that I have ever seen.
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- August 2, 2014 at 2:10 pm
Sarah, I've been on the GSK combo since last August (started one year ago on this day). I believe that the reported progression free survival median is 10.5 months. In my case, the GSK combo dramatically reduced my tumor burden (let's say ballpark 70%) initially. I've been stable since my February scans. (I also worked-in ipi between December and February.)
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- August 3, 2014 at 11:50 am
Unfortunately I am not likely to be a big beacon of hope here. I started the combo in Dec 2013 and had dramatic reduction in size of many of the subQ masses and stabilization of the rest. Over time I had continued reduction in size, but they only lasted 5 months for me before things started growing again. Not all at once, but the tumors that were the last to shrink were the first to grow. My local oncologist rushed to get me into a PD-1 EAP and things moved incredibly quickly. I feel extremely luck to have gotten the care that I have recieved. The PD-1, so far, appears to be working as again subQ masses are shrinking (though they seem to swell for a bit first). I won't have scans until after Labor Day, but I'm crossing my fingers. Last May/early June I had 7 brain mets with possible leptomeningeal disease so had to do WBR last summer. I then had to do SRS for 4 more in January and again for 6 or so in May. The last 2 were while I was on the combo. I have to say Im a bit nervous about the scans in September as I've been having some headaches lately. I think it's just been from overheating and/or dehydration, but it still makes me nervous.
I hope your husband gets a good long time of at least stability or preferably shrinkage/NED with his therapies. Best of luck to you both
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- August 3, 2014 at 1:00 pm
You don't ever need to apologize for being real and for telling your story. I can relate to the fears that accompany the headaches. We have gotten so much more time than we anticipated, @ 24 months from initial diagnosis, which ios a huge amount of time in the lives of our children. We will continue to try to eek out some more time. All the best to you in your journey.
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- August 3, 2014 at 1:00 pm
You don't ever need to apologize for being real and for telling your story. I can relate to the fears that accompany the headaches. We have gotten so much more time than we anticipated, @ 24 months from initial diagnosis, which ios a huge amount of time in the lives of our children. We will continue to try to eek out some more time. All the best to you in your journey.
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- August 3, 2014 at 1:00 pm
You don't ever need to apologize for being real and for telling your story. I can relate to the fears that accompany the headaches. We have gotten so much more time than we anticipated, @ 24 months from initial diagnosis, which ios a huge amount of time in the lives of our children. We will continue to try to eek out some more time. All the best to you in your journey.
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- August 3, 2014 at 11:50 am
Unfortunately I am not likely to be a big beacon of hope here. I started the combo in Dec 2013 and had dramatic reduction in size of many of the subQ masses and stabilization of the rest. Over time I had continued reduction in size, but they only lasted 5 months for me before things started growing again. Not all at once, but the tumors that were the last to shrink were the first to grow. My local oncologist rushed to get me into a PD-1 EAP and things moved incredibly quickly. I feel extremely luck to have gotten the care that I have recieved. The PD-1, so far, appears to be working as again subQ masses are shrinking (though they seem to swell for a bit first). I won't have scans until after Labor Day, but I'm crossing my fingers. Last May/early June I had 7 brain mets with possible leptomeningeal disease so had to do WBR last summer. I then had to do SRS for 4 more in January and again for 6 or so in May. The last 2 were while I was on the combo. I have to say Im a bit nervous about the scans in September as I've been having some headaches lately. I think it's just been from overheating and/or dehydration, but it still makes me nervous.
I hope your husband gets a good long time of at least stability or preferably shrinkage/NED with his therapies. Best of luck to you both
-
- August 3, 2014 at 11:50 am
Unfortunately I am not likely to be a big beacon of hope here. I started the combo in Dec 2013 and had dramatic reduction in size of many of the subQ masses and stabilization of the rest. Over time I had continued reduction in size, but they only lasted 5 months for me before things started growing again. Not all at once, but the tumors that were the last to shrink were the first to grow. My local oncologist rushed to get me into a PD-1 EAP and things moved incredibly quickly. I feel extremely luck to have gotten the care that I have recieved. The PD-1, so far, appears to be working as again subQ masses are shrinking (though they seem to swell for a bit first). I won't have scans until after Labor Day, but I'm crossing my fingers. Last May/early June I had 7 brain mets with possible leptomeningeal disease so had to do WBR last summer. I then had to do SRS for 4 more in January and again for 6 or so in May. The last 2 were while I was on the combo. I have to say Im a bit nervous about the scans in September as I've been having some headaches lately. I think it's just been from overheating and/or dehydration, but it still makes me nervous.
I hope your husband gets a good long time of at least stability or preferably shrinkage/NED with his therapies. Best of luck to you both
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- August 3, 2014 at 8:37 pm
Same thing as described above.
Dx stage IV with high tumor burden in February, on Combo blood improved rapidly, scans in May showing considerable shrinkage, scans in July reval considerable growth 🙁
Next step: Ipi
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- August 6, 2014 at 2:14 pm
I did the Ipi/Yervoy last year and the oncologist deemed it a failure. He started me on Braf/MEK in May. I had a scan last week and out of the 15 internal metasteses I had, 11 are "resolved", 1 shrunk more than 1 cm and the other 4 in my brain are still in question as I'm getting a Brain MRI next week. They were too small to show up on the PET scan.
My Doctor seems to think that the Yervoy is actually helping the Braf/MEK as I had some spots disappear very early on with the Braf/MEK. Either way, the Braf/MEK is definitely working and I'm glad to hear that the expected extension of wellness is 25 months, not just 10.
Good luck to your husband!
Dave
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- August 6, 2014 at 2:14 pm
I did the Ipi/Yervoy last year and the oncologist deemed it a failure. He started me on Braf/MEK in May. I had a scan last week and out of the 15 internal metasteses I had, 11 are "resolved", 1 shrunk more than 1 cm and the other 4 in my brain are still in question as I'm getting a Brain MRI next week. They were too small to show up on the PET scan.
My Doctor seems to think that the Yervoy is actually helping the Braf/MEK as I had some spots disappear very early on with the Braf/MEK. Either way, the Braf/MEK is definitely working and I'm glad to hear that the expected extension of wellness is 25 months, not just 10.
Good luck to your husband!
Dave
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- August 6, 2014 at 2:14 pm
I did the Ipi/Yervoy last year and the oncologist deemed it a failure. He started me on Braf/MEK in May. I had a scan last week and out of the 15 internal metasteses I had, 11 are "resolved", 1 shrunk more than 1 cm and the other 4 in my brain are still in question as I'm getting a Brain MRI next week. They were too small to show up on the PET scan.
My Doctor seems to think that the Yervoy is actually helping the Braf/MEK as I had some spots disappear very early on with the Braf/MEK. Either way, the Braf/MEK is definitely working and I'm glad to hear that the expected extension of wellness is 25 months, not just 10.
Good luck to your husband!
Dave
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- August 9, 2014 at 12:18 am
Just an update here. One new primary melanoma biopsies this week. This is my husband's first new primary since beginning treatment for metastatic melanoma 2 years ago. I know from the side effect profile that it could be related to brag inhibitors. Based on my husband's history of 8 or 9 primary melanomas, it could just as likely be his genes. I lost count of the primaries after we hit 5, but his original dermatologist says from her records this is number 10.
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- August 9, 2014 at 12:18 am
Just an update here. One new primary melanoma biopsies this week. This is my husband's first new primary since beginning treatment for metastatic melanoma 2 years ago. I know from the side effect profile that it could be related to brag inhibitors. Based on my husband's history of 8 or 9 primary melanomas, it could just as likely be his genes. I lost count of the primaries after we hit 5, but his original dermatologist says from her records this is number 10.
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- August 13, 2014 at 7:21 am
Heloo everyone,
My wife’s initial response to the GSK combo was very positive (start on June 14th): she felt better right away, the nodes under her skin (that appeared along with the fever 2 weeks before her due date of June 2nd) disappeared within days, the CT scan a bit under 2 months after the start of the treatment (August 2nd) showed at least 30% decrease in her tumor burden and blood values (hemoglobin and LDH) improved significantly.
However, the last blood test showed increased LDH values which has made us quite anxious/worried. We have heard it could be a false positive, a positive sign (when under therapy when the tumours regress very fast) but probably most likely an early sign of resistance/re-start of growth.
So where we previously thought we were doing good on the combo and had the time to wait until switching to Pembro (announced last week it will become available in Belgium after ipi) or Nivolumab (no news in Europe); it now seems more urgent. Since my wife’s melanoma seems very aggressive (she got sick from one day to the other and this accelerated quickly with nodes appear on a daily basis; she then was in poor shape for 2 weeks just before her due date with very poor blood values) we may not have the time to wait for real progression and wait for ipi and afterwards Pembro to kick in. It seems like we should act soon, now she’s still healthy. Dr. Neyns in Brussels (our second opinion doctor; we saw him last week) also seems to think switching soon may be right but still wants to await one more scan. I’m just afraid that by then the tumor may have grown even more.
So in short, it would be good to see you as after a positive & relatively good period, it seems we’re approaching a critical moment in her treatment choices much earlier than we had expected.
Any advice on recognizing your body's resistence to the BRAF/MEK combo and knowing when to switch to immuno therapy?
Many thanks,
Zoya & Rick
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- August 13, 2014 at 7:21 am
Heloo everyone,
My wife’s initial response to the GSK combo was very positive (start on June 14th): she felt better right away, the nodes under her skin (that appeared along with the fever 2 weeks before her due date of June 2nd) disappeared within days, the CT scan a bit under 2 months after the start of the treatment (August 2nd) showed at least 30% decrease in her tumor burden and blood values (hemoglobin and LDH) improved significantly.
However, the last blood test showed increased LDH values which has made us quite anxious/worried. We have heard it could be a false positive, a positive sign (when under therapy when the tumours regress very fast) but probably most likely an early sign of resistance/re-start of growth.
So where we previously thought we were doing good on the combo and had the time to wait until switching to Pembro (announced last week it will become available in Belgium after ipi) or Nivolumab (no news in Europe); it now seems more urgent. Since my wife’s melanoma seems very aggressive (she got sick from one day to the other and this accelerated quickly with nodes appear on a daily basis; she then was in poor shape for 2 weeks just before her due date with very poor blood values) we may not have the time to wait for real progression and wait for ipi and afterwards Pembro to kick in. It seems like we should act soon, now she’s still healthy. Dr. Neyns in Brussels (our second opinion doctor; we saw him last week) also seems to think switching soon may be right but still wants to await one more scan. I’m just afraid that by then the tumor may have grown even more.
So in short, it would be good to see you as after a positive & relatively good period, it seems we’re approaching a critical moment in her treatment choices much earlier than we had expected.
Any advice on recognizing your body's resistence to the BRAF/MEK combo and knowing when to switch to immuno therapy?
Many thanks,
Zoya & Rick
-
- October 20, 2014 at 9:17 am
Hi everyone,
Short update about my wife's fight with melanoma….
She was diagnosed with Stage IV with heavy tumor load in June 2014 (first CT); started on the combo on the 14th. Her second CT (August) showed >30% reduction in tumor burden. Last week she had her first PET/CT scan and the PET part was fully negative / complete response, HURRAY 🙂 There are still tumors in her liver & spleen, but since we switched hospitals they has some issues with the previous scan results so no comparison could be made yet on the CT side of things. Blood values were also good, with LDH in the normal range. So she's been on the combo for 4 months now, and we hope she can get more mileage out of it.
Our MD mentioned 3 routes:
– Keep going on the combo, next PET in 2 months, blood in a month.
– Keep the Dabrafenib and switch to Ipi (upside: BRAF effect / downside: more side effects without Trametibin).
– Fully switch to Ipi.
His reco at the moment is to keep on the combo at least until the next scan given the positive PET and blood results, so we'll go with that for now & remain vigilant…
Any other thoughts?
Rick
-
- October 20, 2014 at 9:17 am
Hi everyone,
Short update about my wife's fight with melanoma….
She was diagnosed with Stage IV with heavy tumor load in June 2014 (first CT); started on the combo on the 14th. Her second CT (August) showed >30% reduction in tumor burden. Last week she had her first PET/CT scan and the PET part was fully negative / complete response, HURRAY 🙂 There are still tumors in her liver & spleen, but since we switched hospitals they has some issues with the previous scan results so no comparison could be made yet on the CT side of things. Blood values were also good, with LDH in the normal range. So she's been on the combo for 4 months now, and we hope she can get more mileage out of it.
Our MD mentioned 3 routes:
– Keep going on the combo, next PET in 2 months, blood in a month.
– Keep the Dabrafenib and switch to Ipi (upside: BRAF effect / downside: more side effects without Trametibin).
– Fully switch to Ipi.
His reco at the moment is to keep on the combo at least until the next scan given the positive PET and blood results, so we'll go with that for now & remain vigilant…
Any other thoughts?
Rick
-
- October 20, 2014 at 9:17 am
Hi everyone,
Short update about my wife's fight with melanoma….
She was diagnosed with Stage IV with heavy tumor load in June 2014 (first CT); started on the combo on the 14th. Her second CT (August) showed >30% reduction in tumor burden. Last week she had her first PET/CT scan and the PET part was fully negative / complete response, HURRAY 🙂 There are still tumors in her liver & spleen, but since we switched hospitals they has some issues with the previous scan results so no comparison could be made yet on the CT side of things. Blood values were also good, with LDH in the normal range. So she's been on the combo for 4 months now, and we hope she can get more mileage out of it.
Our MD mentioned 3 routes:
– Keep going on the combo, next PET in 2 months, blood in a month.
– Keep the Dabrafenib and switch to Ipi (upside: BRAF effect / downside: more side effects without Trametibin).
– Fully switch to Ipi.
His reco at the moment is to keep on the combo at least until the next scan given the positive PET and blood results, so we'll go with that for now & remain vigilant…
Any other thoughts?
Rick
-
- August 13, 2014 at 7:21 am
Heloo everyone,
My wife’s initial response to the GSK combo was very positive (start on June 14th): she felt better right away, the nodes under her skin (that appeared along with the fever 2 weeks before her due date of June 2nd) disappeared within days, the CT scan a bit under 2 months after the start of the treatment (August 2nd) showed at least 30% decrease in her tumor burden and blood values (hemoglobin and LDH) improved significantly.
However, the last blood test showed increased LDH values which has made us quite anxious/worried. We have heard it could be a false positive, a positive sign (when under therapy when the tumours regress very fast) but probably most likely an early sign of resistance/re-start of growth.
So where we previously thought we were doing good on the combo and had the time to wait until switching to Pembro (announced last week it will become available in Belgium after ipi) or Nivolumab (no news in Europe); it now seems more urgent. Since my wife’s melanoma seems very aggressive (she got sick from one day to the other and this accelerated quickly with nodes appear on a daily basis; she then was in poor shape for 2 weeks just before her due date with very poor blood values) we may not have the time to wait for real progression and wait for ipi and afterwards Pembro to kick in. It seems like we should act soon, now she’s still healthy. Dr. Neyns in Brussels (our second opinion doctor; we saw him last week) also seems to think switching soon may be right but still wants to await one more scan. I’m just afraid that by then the tumor may have grown even more.
So in short, it would be good to see you as after a positive & relatively good period, it seems we’re approaching a critical moment in her treatment choices much earlier than we had expected.
Any advice on recognizing your body's resistence to the BRAF/MEK combo and knowing when to switch to immuno therapy?
Many thanks,
Zoya & Rick
-
- August 9, 2014 at 12:18 am
Just an update here. One new primary melanoma biopsies this week. This is my husband's first new primary since beginning treatment for metastatic melanoma 2 years ago. I know from the side effect profile that it could be related to brag inhibitors. Based on my husband's history of 8 or 9 primary melanomas, it could just as likely be his genes. I lost count of the primaries after we hit 5, but his original dermatologist says from her records this is number 10.
-
- March 17, 2015 at 10:03 pm
Original diagnosis in July 2013, the standard WLE, SLNB and PET cycle have been clean since then. My first two mets (both brain) were discovered 3 weeks ago. One was taken care of through surgery, another through SRT. I only have one small subQ node (have to wait on PET to verify its content).
Most importantly I start on this combo whenever it arrives on my doorstep in the next few days 🙂 Glad to hear that people's experience matches up with what I have been reading and what my oncs have been telling me. I will periodically chime in on this thread with my experience until somebody tells me to shut up 😛
Live long and prosper!
Jeff
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- March 17, 2015 at 10:03 pm
Original diagnosis in July 2013, the standard WLE, SLNB and PET cycle have been clean since then. My first two mets (both brain) were discovered 3 weeks ago. One was taken care of through surgery, another through SRT. I only have one small subQ node (have to wait on PET to verify its content).
Most importantly I start on this combo whenever it arrives on my doorstep in the next few days 🙂 Glad to hear that people's experience matches up with what I have been reading and what my oncs have been telling me. I will periodically chime in on this thread with my experience until somebody tells me to shut up 😛
Live long and prosper!
Jeff
-
- March 17, 2015 at 10:03 pm
Original diagnosis in July 2013, the standard WLE, SLNB and PET cycle have been clean since then. My first two mets (both brain) were discovered 3 weeks ago. One was taken care of through surgery, another through SRT. I only have one small subQ node (have to wait on PET to verify its content).
Most importantly I start on this combo whenever it arrives on my doorstep in the next few days 🙂 Glad to hear that people's experience matches up with what I have been reading and what my oncs have been telling me. I will periodically chime in on this thread with my experience until somebody tells me to shut up 😛
Live long and prosper!
Jeff
-
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