Resistance to Keytruda? Anyone experienced it?

Mel, sorry to hear.  I progressed on Keytruda after about 6 mos of stability and minor reduction.  I was able to return to Braf-Mek (my first Stage IV treatment) for a time in order to make a treatment decision.  During that time I looked at clinical trials (including TIL, which didn't work out for me at the time).  I'm now in the nivo only phase of ipi-nivo (which wasn't available when I progressed on Keytruda).  I'm stable based on scans at week 11.  I'm hoping for continuing stability or better.  If that doesn't work out, I'd likely repeat the same process–look at clinical trials and/or attempt another run on Braf-Mek.  In terms of clinical trials, which I haven't reviewed for a few months, aside from TIL, there is OX-40 and ADC (a targeted chemo), among others. Celeste and Ed have posted about these.  Not generating as much excitement as PD-1, but could be used as bridge treatments.  One additional point–I don't believe that switching from Keytruda to nivo as a single agent is a good solution based on onc discussions.  That said, continuing with Keytruda (which may still be providing a clinical benefit)–pending a change in treatment–should be weighed against your side effects.  Lastly, in onc discussions, I've heard that they've had some limited success with traditional chemo following PD-1–not curative, but as another bridge.

Mel, sorry to hear.  I progressed on Keytruda after about 6 mos of stability and minor reduction.  I was able to return to Braf-Mek (my first Stage IV treatment) for a time in order to make a treatment decision.  During that time I looked at clinical trials (including TIL, which didn't work out for me at the time).  I'm now in the nivo only phase of ipi-nivo (which wasn't available when I progressed on Keytruda).  I'm stable based on scans at week 11.  I'm hoping for continuing stability or better.  If that doesn't work out, I'd likely repeat the same process–look at clinical trials and/or attempt another run on Braf-Mek.  In terms of clinical trials, which I haven't reviewed for a few months, aside from TIL, there is OX-40 and ADC (a targeted chemo), among others. Celeste and Ed have posted about these.  Not generating as much excitement as PD-1, but could be used as bridge treatments.  One additional point–I don't believe that switching from Keytruda to nivo as a single agent is a good solution based on onc discussions.  That said, continuing with Keytruda (which may still be providing a clinical benefit)–pending a change in treatment–should be weighed against your side effects.  Lastly, in onc discussions, I've heard that they've had some limited success with traditional chemo following PD-1–not curative, but as another bridge.

Mel, sorry to hear.  I progressed on Keytruda after about 6 mos of stability and minor reduction.  I was able to return to Braf-Mek (my first Stage IV treatment) for a time in order to make a treatment decision.  During that time I looked at clinical trials (including TIL, which didn't work out for me at the time).  I'm now in the nivo only phase of ipi-nivo (which wasn't available when I progressed on Keytruda).  I'm stable based on scans at week 11.  I'm hoping for continuing stability or better.  If that doesn't work out, I'd likely repeat the same process–look at clinical trials and/or attempt another run on Braf-Mek.  In terms of clinical trials, which I haven't reviewed for a few months, aside from TIL, there is OX-40 and ADC (a targeted chemo), among others. Celeste and Ed have posted about these.  Not generating as much excitement as PD-1, but could be used as bridge treatments.  One additional point–I don't believe that switching from Keytruda to nivo as a single agent is a good solution based on onc discussions.  That said, continuing with Keytruda (which may still be providing a clinical benefit)–pending a change in treatment–should be weighed against your side effects.  Lastly, in onc discussions, I've heard that they've had some limited success with traditional chemo following PD-1–not curative, but as another bridge.

Hi Mel, just wanted to add to what Mat has already given you. There is a Onclive series that has several very good videos about Melanoma and it kind of covers A to Z with some examples of what if this or what if your patients is showing that. Here is a link to first one, https://www.youtube.com/watch?v=eeJp_TKiv54   . I hope you can find some of the answers to what you are looking for. A second video talks about the future and what is looking good.  https://www.youtube.com/watch?v=RIaGfNsG6w4   . I have heard Weber talk about patients switching from one Pd-1 drug to another and getting response. Wishing you the best!!!! Ed

Hi Mel, just wanted to add to what Mat has already given you. There is a Onclive series that has several very good videos about Melanoma and it kind of covers A to Z with some examples of what if this or what if your patients is showing that. Here is a link to first one, https://www.youtube.com/watch?v=eeJp_TKiv54   . I hope you can find some of the answers to what you are looking for. A second video talks about the future and what is looking good.  https://www.youtube.com/watch?v=RIaGfNsG6w4   . I have heard Weber talk about patients switching from one Pd-1 drug to another and getting response. Wishing you the best!!!! Ed

Hi Mel, just wanted to add to what Mat has already given you. There is a Onclive series that has several very good videos about Melanoma and it kind of covers A to Z with some examples of what if this or what if your patients is showing that. Here is a link to first one, https://www.youtube.com/watch?v=eeJp_TKiv54   . I hope you can find some of the answers to what you are looking for. A second video talks about the future and what is looking good.  https://www.youtube.com/watch?v=RIaGfNsG6w4   . I have heard Weber talk about patients switching from one Pd-1 drug to another and getting response. Wishing you the best!!!! Ed

Hi Mel,

It's good you had some response to Keytruda, but the fact you progressed must not be that unusual.  For many, including me, I was a non-responder in the first place.  Going to Nivo (Opdivo) seems like a sideways move since the two drugs work in a very similar pathway though some here may disagree.  Consider the ipi/nivo combo for a more aggressive approach if available.  For me, I responded to neither ipi, or pembro, but together, and with some targeted radiation treatment I have shown the first signs of at least a partial systemic response.  If you can tolerate any side-effects that may emerge from the combo, it seems like a natural next step in treatment.  Best to you in the battle.

Gary

Hi Mel,

It's good you had some response to Keytruda, but the fact you progressed must not be that unusual.  For many, including me, I was a non-responder in the first place.  Going to Nivo (Opdivo) seems like a sideways move since the two drugs work in a very similar pathway though some here may disagree.  Consider the ipi/nivo combo for a more aggressive approach if available.  For me, I responded to neither ipi, or pembro, but together, and with some targeted radiation treatment I have shown the first signs of at least a partial systemic response.  If you can tolerate any side-effects that may emerge from the combo, it seems like a natural next step in treatment.  Best to you in the battle.

Gary

Hi Mel,

It's good you had some response to Keytruda, but the fact you progressed must not be that unusual.  For many, including me, I was a non-responder in the first place.  Going to Nivo (Opdivo) seems like a sideways move since the two drugs work in a very similar pathway though some here may disagree.  Consider the ipi/nivo combo for a more aggressive approach if available.  For me, I responded to neither ipi, or pembro, but together, and with some targeted radiation treatment I have shown the first signs of at least a partial systemic response.  If you can tolerate any side-effects that may emerge from the combo, it seems like a natural next step in treatment.  Best to you in the battle.

Gary