Ipi vs. Nivo or try like mad for the Combo Punch

Hi Rita,

I can tell you what has been working for me. on 9/10/14 my melanoma oncologist told me that a PET from two days prior showed I had mets in lungs, liver and gallbladder. I wanted Keytruda since I had been reading about it here, and knew it was less toxic and had a better response rate than Yervoy. But my doc explained to me that I had to try and fail Yervoy before I could try Keytruda (This was before Opdivo–similar to Keytruda–was approved). I am BRAF-negative, otherwise I would need to have tried, and failed, a targeted BRAF therapy.

What I opted for was the so-called RAD-VAX trial where they zapped one of the lung tumors with 3 high doses of SRS (stereotactic radiation) combined with Yervoy. The hope was to elicit an abscopal effect: radiating the tumor causes the immune system to recognize the residue as an antigen while the Yervoy "takes the brakes off" the immune system.

This did indeed partially work for me. A scan at the end of 2014 revealed that all the tumors except for the gallbladder had stopped growing. I had that removed laproscopically. However a subsequent scan did reveal a new subcutaneous (subq) growing on my left shoulder. So I was switched to Keytruda back at the beginning of the year and have been on it since. I haven't had a scan since then (I will have one next month), but the shoulder appears stable else given the rate it was growing I would have a second head growing out of it by now!

You have to make your own choice but I was guided to mine by the stories and advice that I was given here.

I wish you the best of luck! – Paul

Hi Rita,

I can tell you what has been working for me. on 9/10/14 my melanoma oncologist told me that a PET from two days prior showed I had mets in lungs, liver and gallbladder. I wanted Keytruda since I had been reading about it here, and knew it was less toxic and had a better response rate than Yervoy. But my doc explained to me that I had to try and fail Yervoy before I could try Keytruda (This was before Opdivo–similar to Keytruda–was approved). I am BRAF-negative, otherwise I would need to have tried, and failed, a targeted BRAF therapy.

What I opted for was the so-called RAD-VAX trial where they zapped one of the lung tumors with 3 high doses of SRS (stereotactic radiation) combined with Yervoy. The hope was to elicit an abscopal effect: radiating the tumor causes the immune system to recognize the residue as an antigen while the Yervoy "takes the brakes off" the immune system.

This did indeed partially work for me. A scan at the end of 2014 revealed that all the tumors except for the gallbladder had stopped growing. I had that removed laproscopically. However a subsequent scan did reveal a new subcutaneous (subq) growing on my left shoulder. So I was switched to Keytruda back at the beginning of the year and have been on it since. I haven't had a scan since then (I will have one next month), but the shoulder appears stable else given the rate it was growing I would have a second head growing out of it by now!

You have to make your own choice but I was guided to mine by the stories and advice that I was given here.

I wish you the best of luck! – Paul

Hi Rita,

I can tell you what has been working for me. on 9/10/14 my melanoma oncologist told me that a PET from two days prior showed I had mets in lungs, liver and gallbladder. I wanted Keytruda since I had been reading about it here, and knew it was less toxic and had a better response rate than Yervoy. But my doc explained to me that I had to try and fail Yervoy before I could try Keytruda (This was before Opdivo–similar to Keytruda–was approved). I am BRAF-negative, otherwise I would need to have tried, and failed, a targeted BRAF therapy.

What I opted for was the so-called RAD-VAX trial where they zapped one of the lung tumors with 3 high doses of SRS (stereotactic radiation) combined with Yervoy. The hope was to elicit an abscopal effect: radiating the tumor causes the immune system to recognize the residue as an antigen while the Yervoy "takes the brakes off" the immune system.

This did indeed partially work for me. A scan at the end of 2014 revealed that all the tumors except for the gallbladder had stopped growing. I had that removed laproscopically. However a subsequent scan did reveal a new subcutaneous (subq) growing on my left shoulder. So I was switched to Keytruda back at the beginning of the year and have been on it since. I haven't had a scan since then (I will have one next month), but the shoulder appears stable else given the rate it was growing I would have a second head growing out of it by now!

You have to make your own choice but I was guided to mine by the stories and advice that I was given here.

I wish you the best of luck! – Paul

Hi Rita, glad to hear that you are getting some solid information. Something to think about when it comes to waiting for side effects before starting, is that Ipi(Yervoy takes time to work). If ipi doesn't work and you have to switch to a PD-1 drug, a lot of time will have passed and that time could be very important. Expanded access to combination has the best % chance of working but comes with increased risk of side effects. The Rad Vax (radiation and ipi) treatment that Paul had sounds very interesting and many melanoma specialist have discussed this approach as well as many other combination therapies. Wishing you the best!!! Ed

Hi Rita, glad to hear that you are getting some solid information. Something to think about when it comes to waiting for side effects before starting, is that Ipi(Yervoy takes time to work). If ipi doesn't work and you have to switch to a PD-1 drug, a lot of time will have passed and that time could be very important. Expanded access to combination has the best % chance of working but comes with increased risk of side effects. The Rad Vax (radiation and ipi) treatment that Paul had sounds very interesting and many melanoma specialist have discussed this approach as well as many other combination therapies. Wishing you the best!!! Ed

Hi Rita, glad to hear that you are getting some solid information. Something to think about when it comes to waiting for side effects before starting, is that Ipi(Yervoy takes time to work). If ipi doesn't work and you have to switch to a PD-1 drug, a lot of time will have passed and that time could be very important. Expanded access to combination has the best % chance of working but comes with increased risk of side effects. The Rad Vax (radiation and ipi) treatment that Paul had sounds very interesting and many melanoma specialist have discussed this approach as well as many other combination therapies. Wishing you the best!!! Ed

What about this:

Start with anti PD1 – less risk of side effects, higher response rate than Ipi

In case of progression, switch to Ipi and make sure that the therapy is started immediately. Sequential therapy close in time increases the chances of a response.

Combine with radiotherapy before or during the systemic therapy?

The concurrent Ipi+Nivo combination has the highest response rate but also comes with more side effects.

What about this:

Start with anti PD1 – less risk of side effects, higher response rate than Ipi

In case of progression, switch to Ipi and make sure that the therapy is started immediately. Sequential therapy close in time increases the chances of a response.

Combine with radiotherapy before or during the systemic therapy?

The concurrent Ipi+Nivo combination has the highest response rate but also comes with more side effects.

What about this:

Start with anti PD1 – less risk of side effects, higher response rate than Ipi

In case of progression, switch to Ipi and make sure that the therapy is started immediately. Sequential therapy close in time increases the chances of a response.

Combine with radiotherapy before or during the systemic therapy?

The concurrent Ipi+Nivo combination has the highest response rate but also comes with more side effects.

Rita,

So glad you are working to plow through the info….though it is overwhelming, especially while dealing with a crisis!  Here are some points that may help. 

1.  You've got the response rates about right for the various immunotherapies…but:  Nivo or Keytruda can be tolerated for some folks indefinitely and some have side effects early on and have to be taken off the drugs (though a break from the meds and treatment with steroids often fixes things such that the patients can resume treatment….this is true for ipi as well, though the side effects are usually milder for the anti-PD1 products).  Ipi is given in a set of 4 doses and you are done (although some folks repeat the process if they recur…and some are able to again gain a response…though not as often as folks do with the first round.)  I took Nivo for 2 1/2 years, stopping at that point because that was how the trial was set up.  (I remain NED.)  Keytruda's time span for delivery has been more open ended….often given "until progression".  However, most researchers tend to believe that a more finite quantity of med, over less than 2 years, will prove to be sufficient to both eradicate tumors and create a durable response, in some.  However, we just don't know exactly how long and how much that would be.

2. Durability of response (how long the positive effects of therapy will last, if you gain a response) has not yet been determined for anti-PD1.  Here is a review of durability of response for immunotherapy generally:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/11/review-of-immunotherapy-and-durable.html

3.  Here are some durability figures related to ipi:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/03/ipi-for-melanomathe-data-keeps-pouring.html

http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/11/melanoma-patientsalive-and-kicking-10.html

4.  Yes, the ipi/nivo combo has a much higher response rate.  It also comes with an increased side effect profile.  It is available only in trials. Here too, information regarding durability is still out until we hear it from the ratties. Here is some older comparative data re the Ipi/Nivo combo out of ASCO 2014…but it is still holding true:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/07/nivoipi-combo-nivo-vs-pembro-pd-l1.html 

5.  Then there are the BRAF inhibitors if tumors are BRAF positive. (I don't recall whether your husband's were or not….but since you don't mention that, I'm assuming they are not, but…)  These drugs are different from immunotherapy in that the tumor can actually learn to work around them….in the past within 6-9 months, though now…in combination with MEK inhibitors and intermittent dosing, folks are being well maintained for years.

6.  There is good data that combining radiation with immunotherapy can have a synergistic effect (you can search for info on that on my blog if you like).

7.  Now…for the elephant in the room. Ipi, BRAF and both anti-PD1 products are FDA approved for Stage IV melanoma.  HOWEVER, in order to be given anti-PD1 outside of a trial, the patient must first take and fail ipi as well as BRAFi (if BRAF positive).  It is crazy…but there you go.  While it is conceivable that a doctor could prescribe the drugs in an order of their choosing….it is unlike to occur as insurance coverage follows the FDA approval guidelines.

Hope this helps.  I wish you both my best.  Celeste

Rita,

So glad you are working to plow through the info….though it is overwhelming, especially while dealing with a crisis!  Here are some points that may help. 

1.  You've got the response rates about right for the various immunotherapies…but:  Nivo or Keytruda can be tolerated for some folks indefinitely and some have side effects early on and have to be taken off the drugs (though a break from the meds and treatment with steroids often fixes things such that the patients can resume treatment….this is true for ipi as well, though the side effects are usually milder for the anti-PD1 products).  Ipi is given in a set of 4 doses and you are done (although some folks repeat the process if they recur…and some are able to again gain a response…though not as often as folks do with the first round.)  I took Nivo for 2 1/2 years, stopping at that point because that was how the trial was set up.  (I remain NED.)  Keytruda's time span for delivery has been more open ended….often given "until progression".  However, most researchers tend to believe that a more finite quantity of med, over less than 2 years, will prove to be sufficient to both eradicate tumors and create a durable response, in some.  However, we just don't know exactly how long and how much that would be.

2. Durability of response (how long the positive effects of therapy will last, if you gain a response) has not yet been determined for anti-PD1.  Here is a review of durability of response for immunotherapy generally:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/11/review-of-immunotherapy-and-durable.html

3.  Here are some durability figures related to ipi:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/03/ipi-for-melanomathe-data-keeps-pouring.html

http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/11/melanoma-patientsalive-and-kicking-10.html

4.  Yes, the ipi/nivo combo has a much higher response rate.  It also comes with an increased side effect profile.  It is available only in trials. Here too, information regarding durability is still out until we hear it from the ratties. Here is some older comparative data re the Ipi/Nivo combo out of ASCO 2014…but it is still holding true:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/07/nivoipi-combo-nivo-vs-pembro-pd-l1.html 

5.  Then there are the BRAF inhibitors if tumors are BRAF positive. (I don't recall whether your husband's were or not….but since you don't mention that, I'm assuming they are not, but…)  These drugs are different from immunotherapy in that the tumor can actually learn to work around them….in the past within 6-9 months, though now…in combination with MEK inhibitors and intermittent dosing, folks are being well maintained for years.

6.  There is good data that combining radiation with immunotherapy can have a synergistic effect (you can search for info on that on my blog if you like).

7.  Now…for the elephant in the room. Ipi, BRAF and both anti-PD1 products are FDA approved for Stage IV melanoma.  HOWEVER, in order to be given anti-PD1 outside of a trial, the patient must first take and fail ipi as well as BRAFi (if BRAF positive).  It is crazy…but there you go.  While it is conceivable that a doctor could prescribe the drugs in an order of their choosing….it is unlike to occur as insurance coverage follows the FDA approval guidelines.

Hope this helps.  I wish you both my best.  Celeste

Rita,

So glad you are working to plow through the info….though it is overwhelming, especially while dealing with a crisis!  Here are some points that may help. 

1.  You've got the response rates about right for the various immunotherapies…but:  Nivo or Keytruda can be tolerated for some folks indefinitely and some have side effects early on and have to be taken off the drugs (though a break from the meds and treatment with steroids often fixes things such that the patients can resume treatment….this is true for ipi as well, though the side effects are usually milder for the anti-PD1 products).  Ipi is given in a set of 4 doses and you are done (although some folks repeat the process if they recur…and some are able to again gain a response…though not as often as folks do with the first round.)  I took Nivo for 2 1/2 years, stopping at that point because that was how the trial was set up.  (I remain NED.)  Keytruda's time span for delivery has been more open ended….often given "until progression".  However, most researchers tend to believe that a more finite quantity of med, over less than 2 years, will prove to be sufficient to both eradicate tumors and create a durable response, in some.  However, we just don't know exactly how long and how much that would be.

2. Durability of response (how long the positive effects of therapy will last, if you gain a response) has not yet been determined for anti-PD1.  Here is a review of durability of response for immunotherapy generally:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/11/review-of-immunotherapy-and-durable.html

3.  Here are some durability figures related to ipi:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2015/03/ipi-for-melanomathe-data-keeps-pouring.html

http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/11/melanoma-patientsalive-and-kicking-10.html

4.  Yes, the ipi/nivo combo has a much higher response rate.  It also comes with an increased side effect profile.  It is available only in trials. Here too, information regarding durability is still out until we hear it from the ratties. Here is some older comparative data re the Ipi/Nivo combo out of ASCO 2014…but it is still holding true:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/07/nivoipi-combo-nivo-vs-pembro-pd-l1.html 

5.  Then there are the BRAF inhibitors if tumors are BRAF positive. (I don't recall whether your husband's were or not….but since you don't mention that, I'm assuming they are not, but…)  These drugs are different from immunotherapy in that the tumor can actually learn to work around them….in the past within 6-9 months, though now…in combination with MEK inhibitors and intermittent dosing, folks are being well maintained for years.

6.  There is good data that combining radiation with immunotherapy can have a synergistic effect (you can search for info on that on my blog if you like).

7.  Now…for the elephant in the room. Ipi, BRAF and both anti-PD1 products are FDA approved for Stage IV melanoma.  HOWEVER, in order to be given anti-PD1 outside of a trial, the patient must first take and fail ipi as well as BRAFi (if BRAF positive).  It is crazy…but there you go.  While it is conceivable that a doctor could prescribe the drugs in an order of their choosing….it is unlike to occur as insurance coverage follows the FDA approval guidelines.

Hope this helps.  I wish you both my best.  Celeste

We met with our Melanoma Oncologist yesterday and he shared the results of the combo vs IPI or Nivo and hands down the combo saw better response rates, somewhere around 55-65%. 

We met with our Melanoma Oncologist yesterday and he shared the results of the combo vs IPI or Nivo and hands down the combo saw better response rates, somewhere around 55-65%. 

We met with our Melanoma Oncologist yesterday and he shared the results of the combo vs IPI or Nivo and hands down the combo saw better response rates, somewhere around 55-65%. 

My father is in exactly your position, except that we found a brain met last week. So he had stereotactic radiosurgery on Tuesday…and then if that's stable in 4 weeks we're BACK in your position. I'm a physician myself (though not an oncologist) and I've reviewed a lot of the literature. From what I have learned and in talking with my dad's oncologists, I think that starting with combination treatment is the way to go with some exceptions. If your functional status is good and he can tolerate the toxicity, then the combination ipi/nivo may be the best bet in terms of attacking the melanoma, and it may be worth starting with it because the studies are indicating that it works better in treatment-naive patients. My dad is healthy otherwise, so he is going for it! It's the best thing available right now.

IF we could check the tumor's PD-1 ligand status and if it were positive, then a PD-1 inhibitor (like keytruda or nivolumab) alone is thought to be about as effective as the combination treatment and less toxic. This may be available in the next few months. ALSO, when the ipi/nivo combo is approved for 1st line treatment, as it likely will be, it hopefully won't matter as much if you've already tried one or the other behorehand.

IF for some reason he can't tolerate the toxicity, then it may not be worth the risk.

I see absolutely no reason to start with ipilimumab now given that it's toxicity is higher than the PD-1 inhibitors and the chance of it working is less. 

The combination therapy IS available if you're willing to travel (or if you're lucky enough to have a doctor with availability close by). Here is the clinical trial page – though it is now expanded access – with the sites where the combination is being given:

https://clinicaltrials.gov/show/NCT02186249

My father is in exactly your position, except that we found a brain met last week. So he had stereotactic radiosurgery on Tuesday…and then if that's stable in 4 weeks we're BACK in your position. I'm a physician myself (though not an oncologist) and I've reviewed a lot of the literature. From what I have learned and in talking with my dad's oncologists, I think that starting with combination treatment is the way to go with some exceptions. If your functional status is good and he can tolerate the toxicity, then the combination ipi/nivo may be the best bet in terms of attacking the melanoma, and it may be worth starting with it because the studies are indicating that it works better in treatment-naive patients. My dad is healthy otherwise, so he is going for it! It's the best thing available right now.

IF we could check the tumor's PD-1 ligand status and if it were positive, then a PD-1 inhibitor (like keytruda or nivolumab) alone is thought to be about as effective as the combination treatment and less toxic. This may be available in the next few months. ALSO, when the ipi/nivo combo is approved for 1st line treatment, as it likely will be, it hopefully won't matter as much if you've already tried one or the other behorehand.

IF for some reason he can't tolerate the toxicity, then it may not be worth the risk.

I see absolutely no reason to start with ipilimumab now given that it's toxicity is higher than the PD-1 inhibitors and the chance of it working is less. 

The combination therapy IS available if you're willing to travel (or if you're lucky enough to have a doctor with availability close by). Here is the clinical trial page – though it is now expanded access – with the sites where the combination is being given:

https://clinicaltrials.gov/show/NCT02186249

My father is in exactly your position, except that we found a brain met last week. So he had stereotactic radiosurgery on Tuesday…and then if that's stable in 4 weeks we're BACK in your position. I'm a physician myself (though not an oncologist) and I've reviewed a lot of the literature. From what I have learned and in talking with my dad's oncologists, I think that starting with combination treatment is the way to go with some exceptions. If your functional status is good and he can tolerate the toxicity, then the combination ipi/nivo may be the best bet in terms of attacking the melanoma, and it may be worth starting with it because the studies are indicating that it works better in treatment-naive patients. My dad is healthy otherwise, so he is going for it! It's the best thing available right now.

IF we could check the tumor's PD-1 ligand status and if it were positive, then a PD-1 inhibitor (like keytruda or nivolumab) alone is thought to be about as effective as the combination treatment and less toxic. This may be available in the next few months. ALSO, when the ipi/nivo combo is approved for 1st line treatment, as it likely will be, it hopefully won't matter as much if you've already tried one or the other behorehand.

IF for some reason he can't tolerate the toxicity, then it may not be worth the risk.

I see absolutely no reason to start with ipilimumab now given that it's toxicity is higher than the PD-1 inhibitors and the chance of it working is less. 

The combination therapy IS available if you're willing to travel (or if you're lucky enough to have a doctor with availability close by). Here is the clinical trial page – though it is now expanded access – with the sites where the combination is being given:

https://clinicaltrials.gov/show/NCT02186249

A lot of possibilities here, each one of which I would consider for my own situation, whether it's IPI alone, RadVAX, IP/Nivo combo, etc.

Another possibitliy i would consider is a clinical trial combining PD1 with something other than IPI. I joined one of these in March 2014. More trials are available now than were available then.

As far as combos other than IPI/Nivo, one thought is that IPI and PD1 are both checkpoint inhibitors, in other words they block an interaction between tumor and immune system. Some of the newer PD1 combos combine PD1 (inhibitor) with another agent (OX40, GITR, CD137, etc.) that as I understand them are a kind of accelerator, rather than inhibiting a given checkpoint, they increases/activate one. So it could be thought of as attacking the tumor with 2 different types of mechanisms, rather than two possibly more similar inhibiting agents. The older trial I'm on combines PD1 with another agent that works on natural killer cells, which are a part the body's "other" immune system.

These would be other possible choices, but for my own situation I would consider all of them and would have a hard time weighting the choices for myself, never mind for someone else's situation. The only approach I would be less inclined to consider (for myself) is 'watch and wait' because of how this disease can metastasize.

Good luck with his MRI results, so hopefully you can get going on picking one of these treatment approaches.

A lot of possibilities here, each one of which I would consider for my own situation, whether it's IPI alone, RadVAX, IP/Nivo combo, etc.

Another possibitliy i would consider is a clinical trial combining PD1 with something other than IPI. I joined one of these in March 2014. More trials are available now than were available then.

As far as combos other than IPI/Nivo, one thought is that IPI and PD1 are both checkpoint inhibitors, in other words they block an interaction between tumor and immune system. Some of the newer PD1 combos combine PD1 (inhibitor) with another agent (OX40, GITR, CD137, etc.) that as I understand them are a kind of accelerator, rather than inhibiting a given checkpoint, they increases/activate one. So it could be thought of as attacking the tumor with 2 different types of mechanisms, rather than two possibly more similar inhibiting agents. The older trial I'm on combines PD1 with another agent that works on natural killer cells, which are a part the body's "other" immune system.

These would be other possible choices, but for my own situation I would consider all of them and would have a hard time weighting the choices for myself, never mind for someone else's situation. The only approach I would be less inclined to consider (for myself) is 'watch and wait' because of how this disease can metastasize.

Good luck with his MRI results, so hopefully you can get going on picking one of these treatment approaches.

A lot of possibilities here, each one of which I would consider for my own situation, whether it's IPI alone, RadVAX, IP/Nivo combo, etc.

Another possibitliy i would consider is a clinical trial combining PD1 with something other than IPI. I joined one of these in March 2014. More trials are available now than were available then.

As far as combos other than IPI/Nivo, one thought is that IPI and PD1 are both checkpoint inhibitors, in other words they block an interaction between tumor and immune system. Some of the newer PD1 combos combine PD1 (inhibitor) with another agent (OX40, GITR, CD137, etc.) that as I understand them are a kind of accelerator, rather than inhibiting a given checkpoint, they increases/activate one. So it could be thought of as attacking the tumor with 2 different types of mechanisms, rather than two possibly more similar inhibiting agents. The older trial I'm on combines PD1 with another agent that works on natural killer cells, which are a part the body's "other" immune system.

These would be other possible choices, but for my own situation I would consider all of them and would have a hard time weighting the choices for myself, never mind for someone else's situation. The only approach I would be less inclined to consider (for myself) is 'watch and wait' because of how this disease can metastasize.

Good luck with his MRI results, so hopefully you can get going on picking one of these treatment approaches.

Hi,

I just wanted to throw in my 2 cents worth.  Ipi (Yervoy) does not always take a long time to work.  My husband started it in Mar. 2011 and before he had his 4 infusions in 12 weeks we literally watched his sub q's disappear.

Back to each individual responds differently so don't discount it because someone says it takes a long time to work.  My husband was Stage IV (liver, lungs, unresectable tumor pressing on the Cervical spine and 4 sub q's) in Oc. 2010 and started a clinical trial in Mar. 2011.  He has been NED for over 2.5 years.

Read more about his experience on his profile.

Judy (loving wife of Gene Stage IV and now NED)

Hi,

I just wanted to throw in my 2 cents worth.  Ipi (Yervoy) does not always take a long time to work.  My husband started it in Mar. 2011 and before he had his 4 infusions in 12 weeks we literally watched his sub q's disappear.

Back to each individual responds differently so don't discount it because someone says it takes a long time to work.  My husband was Stage IV (liver, lungs, unresectable tumor pressing on the Cervical spine and 4 sub q's) in Oc. 2010 and started a clinical trial in Mar. 2011.  He has been NED for over 2.5 years.

Read more about his experience on his profile.

Judy (loving wife of Gene Stage IV and now NED)

Hi,

I just wanted to throw in my 2 cents worth.  Ipi (Yervoy) does not always take a long time to work.  My husband started it in Mar. 2011 and before he had his 4 infusions in 12 weeks we literally watched his sub q's disappear.

Back to each individual responds differently so don't discount it because someone says it takes a long time to work.  My husband was Stage IV (liver, lungs, unresectable tumor pressing on the Cervical spine and 4 sub q's) in Oc. 2010 and started a clinical trial in Mar. 2011.  He has been NED for over 2.5 years.

Read more about his experience on his profile.

Judy (loving wife of Gene Stage IV and now NED)