Tafinlar/mekinist and nivolumub all toget

I've seen it done in a trial. At that time though it was the taf Mek plus ipi. I've later seen such a trial talked about with pd1 but not sure if it started yet.

Otherwise if the doc is willing and you are willing to pay for it then it is possible to do. Not something that I'm aware of that is common.

Also combining those meds is probably toxic. That's what happened when they used ipi. That's why it hasn't passed trials yet to get FDA approved as a 3 Med treatment.

Clinicaltrials.gov is where all the trials are in the USA and includes some other countries.

Artie

I've seen it done in a trial. At that time though it was the taf Mek plus ipi. I've later seen such a trial talked about with pd1 but not sure if it started yet.

Otherwise if the doc is willing and you are willing to pay for it then it is possible to do. Not something that I'm aware of that is common.

Also combining those meds is probably toxic. That's what happened when they used ipi. That's why it hasn't passed trials yet to get FDA approved as a 3 Med treatment.

Clinicaltrials.gov is where all the trials are in the USA and includes some other countries.

Artie

I've seen it done in a trial. At that time though it was the taf Mek plus ipi. I've later seen such a trial talked about with pd1 but not sure if it started yet.

Otherwise if the doc is willing and you are willing to pay for it then it is possible to do. Not something that I'm aware of that is common.

Also combining those meds is probably toxic. That's what happened when they used ipi. That's why it hasn't passed trials yet to get FDA approved as a 3 Med treatment.

Clinicaltrials.gov is where all the trials are in the USA and includes some other countries.

Artie

Hayden,

I'd keep pressing your doctor for a combination therapy.  As others mentioned, the combination of drugs with ipi and others had bad side effects for most people, but the PD-1 inhibitors (nivolumab and pembrolizumab) are way easier on most people.  My wife got booted from an ipi/vaccine trial after two doses, but has had no trouble with pembrolizumab, and has had great results with a combination of pembrolizumab and subcutaneous IL-2 injections (at the site after removal of sub-Q lesions).  The IL-2 injections provide a systemic and local response, and we think it has jump-started the PD-1 inhibitors.  

Keep talking with your doctor and asking questions:  If both are individually FDA approved for treatment, is there a specific reason that you can't try them?  Are there any other combination therapies available?  Are there any clinical trials of combination therapies that you're eligible for?

Hayden,

I'd keep pressing your doctor for a combination therapy.  As others mentioned, the combination of drugs with ipi and others had bad side effects for most people, but the PD-1 inhibitors (nivolumab and pembrolizumab) are way easier on most people.  My wife got booted from an ipi/vaccine trial after two doses, but has had no trouble with pembrolizumab, and has had great results with a combination of pembrolizumab and subcutaneous IL-2 injections (at the site after removal of sub-Q lesions).  The IL-2 injections provide a systemic and local response, and we think it has jump-started the PD-1 inhibitors.  

Keep talking with your doctor and asking questions:  If both are individually FDA approved for treatment, is there a specific reason that you can't try them?  Are there any other combination therapies available?  Are there any clinical trials of combination therapies that you're eligible for?

Hayden,

I'd keep pressing your doctor for a combination therapy.  As others mentioned, the combination of drugs with ipi and others had bad side effects for most people, but the PD-1 inhibitors (nivolumab and pembrolizumab) are way easier on most people.  My wife got booted from an ipi/vaccine trial after two doses, but has had no trouble with pembrolizumab, and has had great results with a combination of pembrolizumab and subcutaneous IL-2 injections (at the site after removal of sub-Q lesions).  The IL-2 injections provide a systemic and local response, and we think it has jump-started the PD-1 inhibitors.  

Keep talking with your doctor and asking questions:  If both are individually FDA approved for treatment, is there a specific reason that you can't try them?  Are there any other combination therapies available?  Are there any clinical trials of combination therapies that you're eligible for?

Hayden:

You have tapped into a very important question and one that, unfortunately, is currently unanswerable. As others have said, an early trial of a BRAF inhibitor and ipi resulted in serious liver toxicities. Some researchers believe this is because the trial was designed with drug levels that were too high, and that the combination still has merit. With the anti-PD1 drugs now on the market, the questions all are raised again. 

More pressing is the decision of whether to start combination therapy first or immunotherapy first. A major trial is being launched to look at precisely this question. My sense of what I hear the leading experts say is this:

Targeted therapy is good for rapidly growing disease, to slow things down. Most doctors will continue to give targeted therapy until the tumors show signs of resistance and start growing again. For some patients the tumors never grow again, and the two year survival rate with targeted therapy is not very different from that with immunotherapy. Some data suggests that the length of response can be increased by cycling the drug on and off, but this is still very much a judgment call. I certainly know of several patients who have cycled off targeted therapy after a year or two, then cycled back on.

Immunotherapy does have a larger group of people who have long-term responses, but still that group is not huge. Anti-PD1 is generally more tolerable than ipi and more people respond to it, so most people believe it will become the drug of choice as the first treatment. Currently the anti-PD1 drugs (Keytruda and Opdivo) are only approved for use after a patient has progressed on ipi (Yervoy). This is lilkely to change within the next few weeks and they will be approved for first line therapy. 

All this being said, what about the combination of targeted plus immunotherapy? Again, no-one knows. A paper was published in Nature in December saying that patients only respond to anti-PD1 drugs if they have lymphocytes infiltrated into the tumor microenvironment. We know that ipi can drive lymphocytes into the tumor area, so the idea of treating with ipi first or ipi with an ant-PD1 drug makes some sense.

Studies have also shown that BRAF inhibition drives TIL (tumor-infiltrating lymphocytes) so using an anti-PD1 drug after BRAF inhibition also makes some sense. 

I believe it is very common practice to hold off on the immunotherapy approach until and unless it is needed. Again, more research will hopefully provide more insight. 

The bad news is, we don't really know yet the best ways to use these drugs. The very good new is that we now have a nice handful of effective drugs that can be brought to bear on treating metastatic melanoma. Four years ago we had almost nothing to offer!

Tim–MRF

Hayden:

You have tapped into a very important question and one that, unfortunately, is currently unanswerable. As others have said, an early trial of a BRAF inhibitor and ipi resulted in serious liver toxicities. Some researchers believe this is because the trial was designed with drug levels that were too high, and that the combination still has merit. With the anti-PD1 drugs now on the market, the questions all are raised again. 

More pressing is the decision of whether to start combination therapy first or immunotherapy first. A major trial is being launched to look at precisely this question. My sense of what I hear the leading experts say is this:

Targeted therapy is good for rapidly growing disease, to slow things down. Most doctors will continue to give targeted therapy until the tumors show signs of resistance and start growing again. For some patients the tumors never grow again, and the two year survival rate with targeted therapy is not very different from that with immunotherapy. Some data suggests that the length of response can be increased by cycling the drug on and off, but this is still very much a judgment call. I certainly know of several patients who have cycled off targeted therapy after a year or two, then cycled back on.

Immunotherapy does have a larger group of people who have long-term responses, but still that group is not huge. Anti-PD1 is generally more tolerable than ipi and more people respond to it, so most people believe it will become the drug of choice as the first treatment. Currently the anti-PD1 drugs (Keytruda and Opdivo) are only approved for use after a patient has progressed on ipi (Yervoy). This is lilkely to change within the next few weeks and they will be approved for first line therapy. 

All this being said, what about the combination of targeted plus immunotherapy? Again, no-one knows. A paper was published in Nature in December saying that patients only respond to anti-PD1 drugs if they have lymphocytes infiltrated into the tumor microenvironment. We know that ipi can drive lymphocytes into the tumor area, so the idea of treating with ipi first or ipi with an ant-PD1 drug makes some sense.

Studies have also shown that BRAF inhibition drives TIL (tumor-infiltrating lymphocytes) so using an anti-PD1 drug after BRAF inhibition also makes some sense. 

I believe it is very common practice to hold off on the immunotherapy approach until and unless it is needed. Again, more research will hopefully provide more insight. 

The bad news is, we don't really know yet the best ways to use these drugs. The very good new is that we now have a nice handful of effective drugs that can be brought to bear on treating metastatic melanoma. Four years ago we had almost nothing to offer!

Tim–MRF

Hayden:

You have tapped into a very important question and one that, unfortunately, is currently unanswerable. As others have said, an early trial of a BRAF inhibitor and ipi resulted in serious liver toxicities. Some researchers believe this is because the trial was designed with drug levels that were too high, and that the combination still has merit. With the anti-PD1 drugs now on the market, the questions all are raised again. 

More pressing is the decision of whether to start combination therapy first or immunotherapy first. A major trial is being launched to look at precisely this question. My sense of what I hear the leading experts say is this:

Targeted therapy is good for rapidly growing disease, to slow things down. Most doctors will continue to give targeted therapy until the tumors show signs of resistance and start growing again. For some patients the tumors never grow again, and the two year survival rate with targeted therapy is not very different from that with immunotherapy. Some data suggests that the length of response can be increased by cycling the drug on and off, but this is still very much a judgment call. I certainly know of several patients who have cycled off targeted therapy after a year or two, then cycled back on.

Immunotherapy does have a larger group of people who have long-term responses, but still that group is not huge. Anti-PD1 is generally more tolerable than ipi and more people respond to it, so most people believe it will become the drug of choice as the first treatment. Currently the anti-PD1 drugs (Keytruda and Opdivo) are only approved for use after a patient has progressed on ipi (Yervoy). This is lilkely to change within the next few weeks and they will be approved for first line therapy. 

All this being said, what about the combination of targeted plus immunotherapy? Again, no-one knows. A paper was published in Nature in December saying that patients only respond to anti-PD1 drugs if they have lymphocytes infiltrated into the tumor microenvironment. We know that ipi can drive lymphocytes into the tumor area, so the idea of treating with ipi first or ipi with an ant-PD1 drug makes some sense.

Studies have also shown that BRAF inhibition drives TIL (tumor-infiltrating lymphocytes) so using an anti-PD1 drug after BRAF inhibition also makes some sense. 

I believe it is very common practice to hold off on the immunotherapy approach until and unless it is needed. Again, more research will hopefully provide more insight. 

The bad news is, we don't really know yet the best ways to use these drugs. The very good new is that we now have a nice handful of effective drugs that can be brought to bear on treating metastatic melanoma. Four years ago we had almost nothing to offer!

Tim–MRF