I don't have pancreatic cancer, but I have taken Keytruda (for endometrial cancer) and have some thoughts, some of which are fairly cynical.
Keytruda, and other related "immune checkpoint inhibitors", can be true miracle drugs in certain situations. These are mostly in cancers that have high levels of new mutations that are only in the cancer (aka somatic mutations). Examples include melanomas (mutations from sun damage), lung cancers (especially in smokers), bladder cancers, and cancers that are defective in a DNA repair activity called mismatch repair (MMR). MMR is defective in cancers of people with Lynch syndrome, as well as in many non-Lynch cancers, particularly colorectal and endometrial. However, Keytruda does sometimes still work in cancers with very low levels of new mutations. Most pancreatic cancers have low levels of mutations (listed on sequencing reports as TMB. Less than "10" is low.)
But Keytruda is also sold by a capitalist enterprise (Merck) that is seeking to maximize profit. Their goal is to put as many people on Keytruda as possible, whether or not it's going to do them any good. (My hospital sends the insurance company a $56,000 bill on days I have a Keytruda infusion, including $40,000 for the Keytruda. The insurance company sends them $17,000 in total.)
In their initial clinical trials, Merck did try to distinguish between people who would benefit from Keytruda and those who would not, but more recently they have made minimal effort in this regard. In the endometrial cancer trials, they did distinguish between MMR deficient cancers (where it works great), and MMR proficient cancers (where it works poorly, but there is a statistically significant improvement in a fraction of patients.). But they made no attempt to determine which MMR proficient patients might benefit, and the FDA has now approved Keytruda for MMR proficient endometrial cancers in combination with two different sets of drugs. These are now standard of care for recurrent MMR proficient endometrial cancers, such as mine, even though they work very poorly in the majority of these patients. I have progressed while still on the first Keytruda drug combination, but, wouldn't you know, my doctors now want me to try the second one. Merck is looking golden, however.
I haven't had any side effects from the Keytruda, but some patients do, and you should consider that as well.
Before I started taking Keytruda, I thought it was very unlikely that I would benefit (for reasons I won't go into), but I figured that there was some hope that I would, and that the risk of harm was fairly low. And I'm not the one paying $17,000 every 3 weeks. So I did it.
Is it possible for you to take Olaparib alone outside the clinical trial? Or is the trial the only way for you to get Olaparib?
@val64 - building on your comment, I, too, am taking pembro for stage IVB endometrial cancer (with mets to lungs). The difference between us is that my cancer is MMR deficient. I also have a high TMB level. After only 3 chemo/pembro infusions, I am NED. 6 lung tumors disappeared. I start maintenance with pembro alone next week.
My oncologist and I are tiptoeing gently into maintenance because pembro has been rough on me. The scariest adverse event (AE) has been the effect on my vision. Last week I asked my onc how many other patients in his practice had the same AE. He said "none." He then added that at any given time, 50% of folks in the infusion room are getting pembro. This is a large suburban practice outside a major metro area, part of a comprehensive cancer center (or whatever they call the tippy-top designation for cancer treatment). Merck is indeed making bank.
I completely trust my onc, and believe he has my best interests foremost in his treatment plan, but we patients should also be aware that many oncologists get a percentage of the billing for infusion drugs. My most recent billing for infusion was just over $40K.
I don't have pancreatic cancer, but I have taken Keytruda (for endometrial cancer) and have some thoughts, some of which are fairly cynical.
Keytruda, and other related "immune checkpoint inhibitors", can be true miracle drugs in certain situations. These are mostly in cancers that have high levels of new mutations that are only in the cancer (aka somatic mutations). Examples include melanomas (mutations from sun damage), lung cancers (especially in smokers), bladder cancers, and cancers that are defective in a DNA repair activity called mismatch repair (MMR). MMR is defective in cancers of people with Lynch syndrome, as well as in many non-Lynch cancers, particularly colorectal and endometrial. However, Keytruda does sometimes still work in cancers with very low levels of new mutations. Most pancreatic cancers have low levels of mutations (listed on sequencing reports as TMB. Less than "10" is low.)
But Keytruda is also sold by a capitalist enterprise (Merck) that is seeking to maximize profit. Their goal is to put as many people on Keytruda as possible, whether or not it's going to do them any good. (My hospital sends the insurance company a $56,000 bill on days I have a Keytruda infusion, including $40,000 for the Keytruda. The insurance company sends them $17,000 in total.)
In their initial clinical trials, Merck did try to distinguish between people who would benefit from Keytruda and those who would not, but more recently they have made minimal effort in this regard. In the endometrial cancer trials, they did distinguish between MMR deficient cancers (where it works great), and MMR proficient cancers (where it works poorly, but there is a statistically significant improvement in a fraction of patients.). But they made no attempt to determine which MMR proficient patients might benefit, and the FDA has now approved Keytruda for MMR proficient endometrial cancers in combination with two different sets of drugs. These are now standard of care for recurrent MMR proficient endometrial cancers, such as mine, even though they work very poorly in the majority of these patients. I have progressed while still on the first Keytruda drug combination, but, wouldn't you know, my doctors now want me to try the second one. Merck is looking golden, however.
I haven't had any side effects from the Keytruda, but some patients do, and you should consider that as well.
Before I started taking Keytruda, I thought it was very unlikely that I would benefit (for reasons I won't go into), but I figured that there was some hope that I would, and that the risk of harm was fairly low. And I'm not the one paying $17,000 every 3 weeks. So I did it.
Is it possible for you to take Olaparib alone outside the clinical trial? Or is the trial the only way for you to get Olaparib?
I’m glad you didn’t have side effects. I’m somewhat spoiled, having practically none during six months of chemo at UCLA. Progressively more fatigued as my blood tests slowly decay cycle after cycle, but no pain or nausea.
I do believe I would be switching to olaparib by itself anyway now, that was always the plan. But I don’t know if I can get into the study later or have to do that at this juncture if ever (I am already running into an exclusion criterion since I have had chemo for the maximum acceptable of six months).
I assume BRCA/BRCA2 are not “mismatch repair” mutations? I never heard my oncologist mention MMR (and my genetic profile had nothing “actionable” but BRCA2).
My oncologist recommended I sign up for a study giving this on top of oleaparib (for BRCA mutation PDAC after first line chemo).
Any experiences with Keytruda? Is it automatically a good idea to add immunotherapy? I don’t know why this would be particularly appropriate for BRCA mutations.
You're correct that BRCA1 and 2 are not mismatch repair genes. As far as I know, mutations in them do not cause a high TMB.
They probably want people joining the clinical trial immediately as they come off chemo, so that they can randomize them to Olaparib alone or Olaparib plus Keytruda.
Hopefully the Olaparib, with or without the Keytruda, will work for you.
@val64 - building on your comment, I, too, am taking pembro for stage IVB endometrial cancer (with mets to lungs). The difference between us is that my cancer is MMR deficient. I also have a high TMB level. After only 3 chemo/pembro infusions, I am NED. 6 lung tumors disappeared. I start maintenance with pembro alone next week.
My oncologist and I are tiptoeing gently into maintenance because pembro has been rough on me. The scariest adverse event (AE) has been the effect on my vision. Last week I asked my onc how many other patients in his practice had the same AE. He said "none." He then added that at any given time, 50% of folks in the infusion room are getting pembro. This is a large suburban practice outside a major metro area, part of a comprehensive cancer center (or whatever they call the tippy-top designation for cancer treatment). Merck is indeed making bank.
I completely trust my onc, and believe he has my best interests foremost in his treatment plan, but we patients should also be aware that many oncologists get a percentage of the billing for infusion drugs. My most recent billing for infusion was just over $40K.
Good luck, OP
Thank you.
I’m glad you didn’t have side effects. I’m somewhat spoiled, having practically none during six months of chemo at UCLA. Progressively more fatigued as my blood tests slowly decay cycle after cycle, but no pain or nausea.
I do believe I would be switching to olaparib by itself anyway now, that was always the plan. But I don’t know if I can get into the study later or have to do that at this juncture if ever (I am already running into an exclusion criterion since I have had chemo for the maximum acceptable of six months).
I assume BRCA/BRCA2 are not “mismatch repair” mutations? I never heard my oncologist mention MMR (and my genetic profile had nothing “actionable” but BRCA2).
Hoping you are doing well!
You're correct that BRCA1 and 2 are not mismatch repair genes. As far as I know, mutations in them do not cause a high TMB.
They probably want people joining the clinical trial immediately as they come off chemo, so that they can randomize them to Olaparib alone or Olaparib plus Keytruda.
Hopefully the Olaparib, with or without the Keytruda, will work for you.