1. < Pancreatic Cancer

Negative Turn in a Long Journey

Posted by wpprescott @wpprescott, 4 days ago

I was diagnosed with PC in March 2023 just after my 60th birthday, and have frequently checked this forum, read most of the posts and responses here, and have taken great comfort and learned a lot from everyone's input. I am at an important crossroads in my treatment, however, and would appreciate any thoughts, advice and input you all may have. I am being treated at Smilow Cancer Hospital at Yale.

I had a small (1.9 cm) tumor in the head of my pancreas that restricted my bile duct and was also wrapped around the portal vein. I had 8 rounds of Folfirinox, the tumor shrunk away from the vein, and I was on the table for Whipple surgery on 9/25/23.

At the start of surgery, 5 small malignant lesions were found on my liver (even though nothing was ever seen on scans) and surgery was aborted. I started FFOX again and sought second opinions at UCLA, Mayo Clinic, and Frodetert/MCW which provided a lot of motivation for me to push on towards making surgery possible again. After 14 more rounds of FFOX (22 total) I was back on the table one day short of a year later on 9/24/24 for Whipple. This time it was a success. Eight hours of Whipple followed by 4 hours of portal vein reconstruction. I recovered very quickly (only 4 days in the hospital) and within 2 months was back to “normal” with only a few minor digestive issues to deal with.

My post-surgery pathology was as follows: Tumor: 1.5 cm, Grade G2, invades retroperitoneal soft tissue and portal vein. Perineural invasion present. Involves vascular bed/groove (corresponding to superior mesenteric vein/portal vein). All margins uninvolved by invasive carcinoma and high-grade intraepithelial neoplasia. 24 lymph nodes examined; 1 involved. Staging: ypT1c N1, at least Stage IIB. Tumor testing showed I have the KRAS G12D mutation.

My “secret weapon” throughout all this has been my physical health. I was a competitive cyclist and runner for over 40 years and I had very mild side effects during the 22 rounds of chemo; always ECOG=0. Throughout the last 2+ years I have continued to ride my bike, walk, jog, swim and do the occasional weight workout or yoga, on average about 10-15 hrs./week.

As you can probably guess, things have taken a negative turn recently. My first two sets of post-surgery check-up scans were NED but a May CT scan showed (and a PET scan confirmed) suspicious areas–soft tissue attenuation around the celiac/hepatic arteries, thickening of the left adrenal gland, an enlarged lymph node adjacent to the superior mesenteric vein, and a small lump in the wall of my abdomen. The lump appeared 2-3 months after surgery and is right at the incision where one of my abdominal drains exited. I had it checked out back in January and it was deemed scar tissue. I am having it biopsied tomorrow so at least I’ll know if that's the case.

So finally to ask my question(s). Where do I go from here? My options at Yale are a drug trial or back to chemo: either FFOX or Gem-Nab. I know what living for Folfirinox is like but also know the side effects of Gem-Nab might be even more tolerable. My oncologist said normally she would recommend Gem-Nab but since I haven’t had treatment for over a year (last round of FFOX was May 2024) that it’s “up to me”.

There is a KRAS G12D drug trial at Yale (ASP 3082) that I hoped to get into but there’s no space right now. I am still waiting to hear if Yale has other KRAS trials available. I have a list of other trial options at MSK and Dana-Farber since both locations are relatively close by. I would be willing to travel even farther afield for a trial if I could manage it.

Thanks for taking the time to read my story and for any thoughts, personal experiences or other things you have to share.

Interested in more discussions like this? Go to the Pancreatic Cancer Support Group.

bradthompson88 | @bradthompson88 | 4 days ago

Can you do fulfirinox and also the kras trial if you would
Get in?

With not too much side effects, id go with what worked before until
It stops working.

I start my first round Monday.

I hear this stuff comes back but am inspired that you beat it back down so you could have surgery. I was at 2b until the PET scan showed liver tumors.

REPLY
joiedevivre | @joiedevivre | 4 days ago

@wpprescott My husband's oncologist told us that if there is standard-of-care chemotherapy still available, do that first. According to onco, trials are last options, although I hear of people going for trials in the hope of a more permanent 'fix'. Right now it seems you have either Folfirinox or Gem-Nab. My husband found Folfirinox harder and his markers climbed. Onco switched to Gem-Abraxane and my husband was on it for 15 months - side effects minimal and tolerable. He managed to make 3 short trips (including flying 6 hours) during that time. Now he has localised recurrence at the resected edge of pancreas. Onco said this is indication of the cancer's resistance to Gem-Abraxane so onco switched to a combination of VMAT and Capecitabine. This cancer journey is not a straight level road unfortunately but the thing is to grit our teeth and move forward. You HAVE OPTIONS - that has to be good.

REPLY
1 reply
markymarkfl | @markymarkfl | 4 days ago

@bradthompson88 , @wpprescott would not be able to do any other SOC cancer treatment simultaneously with trial drugs. The trials are super-regulated to make sure only the trial drug itself is or is not contributing to the patient's response. They also want to know about and approve/reject any complementary or alternative meds (herbs, OTC, etc) you take on a regular basis so they can rule out their impact on trial drug response as well.

@wpprescott , I'm sorry to hear about your dilemma, but it sounds like you do have options. I also have the KRAS G12D mutation. I had the option to start on a pan-RAS trial drug a month ago, but it was too much travel, and I lost my slot while weighing my options. The same trial (and another similar one) was supposed to open up closer to home, but they have not materialized. 🙁

Among the "RAS" related mutations, there are NRAS and KRAS families, and then specific variants (like G12D) within them. The "pan-RAS" drugs (like RMC-6236) target the whole family, sort of like a shotgun, but may have more side effects because of the wide targeting. The more variant-specific drugs (like RMC-9805) are said to have fewer side effects because of their more precise targeting. Both types are getting relatively good reviews so far, but both are still so early in development that it's hard to say how effective or long-lasting they will be.

In my case, I also have a germline ATM mutation. In asking around, 5 different oncologists have emphasized to me how a KRAS mutation is the driver in so many pancreatic cancers that it's the best thing to target first if you have a choice.

MSK offered me one trial that didn't target either of my mutations, so I passed on that one. If they can get you into a pan-RAS or KRAS G12D trial that close to home, it sounds like the ideal choice.

My pre-Whipple response to Folfirinox was pretty ho-hum. After my post-Whipple recurrence, I started Gemcitabine + Abraxane + Cisplatin. Everyone is different, but I got a much more robust response (in terms of CA19-9 and MRI) to it than Folfirinox, with far fewer treatment side effects. I got about 15 months of good control from it before drug resistance started to develop.

So, until I get into the right trial, the same 5 oncologists mentioned above have also recommended I try the one SoC drug I haven't already tried: Onyvide (nano-liposomal irinotecan, aka Naliri).

Although I had "regular" irinotecan as part of my Folfirinox, the Naliri formulation is supposed to penetrate tumors better. I will get it with Leucovorin and 5-FU (ingredients also in Folfirinox), but without the Oxaliplatin. The thought process is that after so long on Cisplatin, I might be drug-resistant to platins in general, and skipping the Oxaliplatin will give me time to recover from all the Abraxane-induced peripheral neuropathy.

Those are basically all the options on the table I know of, unless you have other targetable mutations or an oncologist willing to go outside the box and try another drug off-label. There's a lot of research and $$$ going into RAS-related trials right now, so that seems like a good place to focus your trial search.

As an aside, there are other targetable properties of cancers that aren't necessarily gene mutations. Cancer cells may express certain proteins that can be recognized by certain "antibodies" which would carry a cytotoxic payload to the cancer cells. CLDN18.2, TROP2, and Mesothelin are three that I'm aware of. Sometimes the payload is standard chemo drug (making it an ADC -- Antibody/Drug Conjugate), or it could be a "cellular therapy" where living immune cells do the killing.

There's a newer trial going on at MD Anderson going on right now, in which CAR-NK (Natural Killer) cells engineered to recognize TROP2 are injected by IV. It's attractive (one shot and done), but I don't qualify because of the similar trial/treatment I did last year (the same cells, but injected into my peritoneal space rather than intravenously. It's hard to tell whether they work better as an IV than in peritoneum, but failure of the latter is why I'm still a mess today. That's always a risk with trials...

Wishing you the best with your decision and treatment!

--mm

REPLY
1 reply
marienewland | @mnewland99 | 4 days ago
In reply to @joiedevivre "@wpprescott My husband's oncologist told us that if there is standard-of-care chemotherapy still available, do that..." + (show)
@joiedevivre

@wpprescott My husband's oncologist told us that if there is standard-of-care chemotherapy still available, do that first. According to onco, trials are last options, although I hear of people going for trials in the hope of a more permanent 'fix'. Right now it seems you have either Folfirinox or Gem-Nab. My husband found Folfirinox harder and his markers climbed. Onco switched to Gem-Abraxane and my husband was on it for 15 months - side effects minimal and tolerable. He managed to make 3 short trips (including flying 6 hours) during that time. Now he has localised recurrence at the resected edge of pancreas. Onco said this is indication of the cancer's resistance to Gem-Abraxane so onco switched to a combination of VMAT and Capecitabine. This cancer journey is not a straight level road unfortunately but the thing is to grit our teeth and move forward. You HAVE OPTIONS - that has to be good.

Jump to this post

You name some chemo regimens that I'm not familiar with: Gem-Nab and VMAT. Do you know if these are for your husband's particular mutation which I think you said was G12V? Wishing you @joiedevivre anf your husband success.

REPLY
1 reply
marienewland | @mnewland99 | 4 days ago
In reply to @markymarkfl "@bradthompson88 , @wpprescott would not be able to do any other SOC cancer treatment simultaneously with..." + (show)
@markymarkfl

@bradthompson88 , @wpprescott would not be able to do any other SOC cancer treatment simultaneously with trial drugs. The trials are super-regulated to make sure only the trial drug itself is or is not contributing to the patient's response. They also want to know about and approve/reject any complementary or alternative meds (herbs, OTC, etc) you take on a regular basis so they can rule out their impact on trial drug response as well.

@wpprescott , I'm sorry to hear about your dilemma, but it sounds like you do have options. I also have the KRAS G12D mutation. I had the option to start on a pan-RAS trial drug a month ago, but it was too much travel, and I lost my slot while weighing my options. The same trial (and another similar one) was supposed to open up closer to home, but they have not materialized. 🙁

Among the "RAS" related mutations, there are NRAS and KRAS families, and then specific variants (like G12D) within them. The "pan-RAS" drugs (like RMC-6236) target the whole family, sort of like a shotgun, but may have more side effects because of the wide targeting. The more variant-specific drugs (like RMC-9805) are said to have fewer side effects because of their more precise targeting. Both types are getting relatively good reviews so far, but both are still so early in development that it's hard to say how effective or long-lasting they will be.

In my case, I also have a germline ATM mutation. In asking around, 5 different oncologists have emphasized to me how a KRAS mutation is the driver in so many pancreatic cancers that it's the best thing to target first if you have a choice.

MSK offered me one trial that didn't target either of my mutations, so I passed on that one. If they can get you into a pan-RAS or KRAS G12D trial that close to home, it sounds like the ideal choice.

My pre-Whipple response to Folfirinox was pretty ho-hum. After my post-Whipple recurrence, I started Gemcitabine + Abraxane + Cisplatin. Everyone is different, but I got a much more robust response (in terms of CA19-9 and MRI) to it than Folfirinox, with far fewer treatment side effects. I got about 15 months of good control from it before drug resistance started to develop.

So, until I get into the right trial, the same 5 oncologists mentioned above have also recommended I try the one SoC drug I haven't already tried: Onyvide (nano-liposomal irinotecan, aka Naliri).

Although I had "regular" irinotecan as part of my Folfirinox, the Naliri formulation is supposed to penetrate tumors better. I will get it with Leucovorin and 5-FU (ingredients also in Folfirinox), but without the Oxaliplatin. The thought process is that after so long on Cisplatin, I might be drug-resistant to platins in general, and skipping the Oxaliplatin will give me time to recover from all the Abraxane-induced peripheral neuropathy.

Those are basically all the options on the table I know of, unless you have other targetable mutations or an oncologist willing to go outside the box and try another drug off-label. There's a lot of research and $$$ going into RAS-related trials right now, so that seems like a good place to focus your trial search.

As an aside, there are other targetable properties of cancers that aren't necessarily gene mutations. Cancer cells may express certain proteins that can be recognized by certain "antibodies" which would carry a cytotoxic payload to the cancer cells. CLDN18.2, TROP2, and Mesothelin are three that I'm aware of. Sometimes the payload is standard chemo drug (making it an ADC -- Antibody/Drug Conjugate), or it could be a "cellular therapy" where living immune cells do the killing.

There's a newer trial going on at MD Anderson going on right now, in which CAR-NK (Natural Killer) cells engineered to recognize TROP2 are injected by IV. It's attractive (one shot and done), but I don't qualify because of the similar trial/treatment I did last year (the same cells, but injected into my peritoneal space rather than intravenously. It's hard to tell whether they work better as an IV than in peritoneum, but failure of the latter is why I'm still a mess today. That's always a risk with trials...

Wishing you the best with your decision and treatment!

--mm

Jump to this post

As always @markymarkfl, a stellar summary of chemo drugs and options. Always a delicate subject about clinical trials, i.e., head first into them or are they a last resort; certainly a personal decision. You must be scheduled for your Naliri treatment by now? I hope it works for you. I have my ultrasound today to see if I'm still a candidate for histotripsy; however, I do have those nasty peritoneal nodules now. I have no idea what their status is. Do you have a recommendation on how to best to view them?
For being a "mess", your critical and analytical thinking skills are way above most of us. Wishing you the best in Naliri.

REPLY
gracect | @gracect | 3 days ago

I would go to MSK immediately. They have so very many more trials than Yale and many more KRAS trials going on. We also attribute my husband’s survival partially to his exercise - he was in great shape until this hit out of nowhere -has started his 4th year on Gemabraxane regimen, now biweekly. There was a trial drug added in the very beginning that didn’t pan out. But he has been Stage 4 metastasized to the liver since the beginning. We believe the main tumor in the tail was killed by radiation back in February, something that they didn’t believe possible until early this year. As you know, all the latest science is not available at Yale first. And it can take forever to get scans and tests, etc. Not so at MSK. Just dive in. As you know, time is of the essence. You’ve been through so much already. Gods Bless
Also, they are very willing to tell you where another trial is available if they think it’s the one for you.

REPLY
1 reply
marienewland | @mnewland99 | 3 days ago
In reply to @gracect "I would go to MSK immediately. They have so very many more trials than Yale and..." + (show)
@gracect

I would go to MSK immediately. They have so very many more trials than Yale and many more KRAS trials going on. We also attribute my husband’s survival partially to his exercise - he was in great shape until this hit out of nowhere -has started his 4th year on Gemabraxane regimen, now biweekly. There was a trial drug added in the very beginning that didn’t pan out. But he has been Stage 4 metastasized to the liver since the beginning. We believe the main tumor in the tail was killed by radiation back in February, something that they didn’t believe possible until early this year. As you know, all the latest science is not available at Yale first. And it can take forever to get scans and tests, etc. Not so at MSK. Just dive in. As you know, time is of the essence. You’ve been through so much already. Gods Bless
Also, they are very willing to tell you where another trial is available if they think it’s the one for you.

Jump to this post

Good advice @gracect. MSK would be my choice also, if I lived on the east coast. Did your husband have a targeted radiation like MRIdean, or the generalized radiation? Did he avoid neuropathy being on the gemabraxane, and do you know and are willing to share his mutations? Lots of questions, but 4 years on that chemo regimen is incredible! I think @199 has been on that long term, also.

REPLY
2 replies
wpprescott | @wpprescott | 3 days ago

Thank you everyone for exactly what I expected! Insightful, thoughtful, helpful and supportive comments and ideas. And I second the kudos for @markymarkfl for the detailed drug/chemo thoughts. You are a gold mine of information and I have admired your input over the last couple years of following this forum, along with @mnewland99, @stageivsurvivor and others too numerous to mention.

A couple more details and thoughts and an update on my upcoming week. I forgot to mention that all along my PC journey I have been a CA 19-9 and CEA "non-producer". My CA 19-9 was 20 at its highest and is currently < 9. My CEA was 9.9 back at my diagnosis but dropped after I started chemo and has been in the 3-5 range for the most part since then. It did increase to 7.7 when I had my last check, which raised some concern with my oncologist. I have also had a lot of "funny" scans over time which have initially been a bit concerning only to be a blip on the screen and nothing major or consistent. I attribute that partly to my activity level--my body is always active and it seems like a lot of things that show up on scans are just inflammation or temporary but benign changes masquerading as something more sinister. As I often say "someone has to be 3 standard deviations away from the mean and it seems like that is always me!"

As I mentioned I have a biopsy of the lump on my abdomen tomorrow, I am having a CT scan Friday to check to check for changes since my "bad" scan on 5/28, and hope to hear more today about possible KRAS G12D (or pan-KRAS) trials at Yale. If the biopsy and scan confirm malignancy and there are no immediate trial option, I'm leaning towards trying Gem-Nab as opposed to more FFOX. I can always go back to FFOX if G-N doesn't work and I can also keep looking for a trial and stop chemo to start that. I meet with my oncologist a week from today and hopefully I'll have a clear plan then.

@gracect If you don't mind, I'm going to send you a DM to chat about your experiences with Yale vs. MSK. I'd love to learn more about the logistics/location of your husband's treatment at MSK.

REPLY
4 replies
plum1 | @plum1 | 3 days ago
In reply to @wpprescott "Thank you everyone for exactly what I expected! Insightful, thoughtful, helpful and supportive comments and ideas...." + (show)
@wpprescott

Thank you everyone for exactly what I expected! Insightful, thoughtful, helpful and supportive comments and ideas. And I second the kudos for @markymarkfl for the detailed drug/chemo thoughts. You are a gold mine of information and I have admired your input over the last couple years of following this forum, along with @mnewland99, @stageivsurvivor and others too numerous to mention.

A couple more details and thoughts and an update on my upcoming week. I forgot to mention that all along my PC journey I have been a CA 19-9 and CEA "non-producer". My CA 19-9 was 20 at its highest and is currently < 9. My CEA was 9.9 back at my diagnosis but dropped after I started chemo and has been in the 3-5 range for the most part since then. It did increase to 7.7 when I had my last check, which raised some concern with my oncologist. I have also had a lot of "funny" scans over time which have initially been a bit concerning only to be a blip on the screen and nothing major or consistent. I attribute that partly to my activity level--my body is always active and it seems like a lot of things that show up on scans are just inflammation or temporary but benign changes masquerading as something more sinister. As I often say "someone has to be 3 standard deviations away from the mean and it seems like that is always me!"

As I mentioned I have a biopsy of the lump on my abdomen tomorrow, I am having a CT scan Friday to check to check for changes since my "bad" scan on 5/28, and hope to hear more today about possible KRAS G12D (or pan-KRAS) trials at Yale. If the biopsy and scan confirm malignancy and there are no immediate trial option, I'm leaning towards trying Gem-Nab as opposed to more FFOX. I can always go back to FFOX if G-N doesn't work and I can also keep looking for a trial and stop chemo to start that. I meet with my oncologist a week from today and hopefully I'll have a clear plan then.

@gracect If you don't mind, I'm going to send you a DM to chat about your experiences with Yale vs. MSK. I'd love to learn more about the logistics/location of your husband's treatment at MSK.

Jump to this post

I’d recommend looking for a trial - my oncologist didn’t want me to start chemo and recommended looking - I’ve been able to defer chemo for a year by going into the RMC doublet trial (6236+9805) which has been effective so far. We do have to travel across country every three weeks as it was difficult to find a slot but it’s been worth it.

REPLY
199 | @199 | 3 days ago
In reply to @mnewland99 "Good advice @gracect. MSK would be my choice also, if I lived on the east coast...." + (show)
@mnewland99

Good advice @gracect. MSK would be my choice also, if I lived on the east coast. Did your husband have a targeted radiation like MRIdean, or the generalized radiation? Did he avoid neuropathy being on the gemabraxane, and do you know and are willing to share his mutations? Lots of questions, but 4 years on that chemo regimen is incredible! I think @199 has been on that long term, also.

Jump to this post

I will celebrate 3 years on Abraxane & Gemczar on 22 July. 74 total treatments with 4 months off so 44/now +30 on the 17th of July 🙂 I wish I had known about acupuncture when I first started chemo. I think it helps my neuropathy but wonder if it would be much less if I had acupunctures early on. I have the KRAS G12D and TP53 mutations. My latest scan was "stable" and my CA19-9 was 49.5.

REPLY
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